Cosmeceutical and Dermatological Potential of Olive Mill Wastewater: A Sustainable and Eco-Friendly Source of Natural Ingredients

Abstract

Olive oil and its derivatives, particularly polyphenol-rich extracts, are valued for their antioxidant, anti-inflammatory, and regenerative properties. Olive mill wastewater (OMWW), a byproduct of olive oil production, traditionally seen as an environmental pollutant, has emerged as a promising source of high-value dermatological ingredients. Key polyphenols such as hydroxytyrosol, oleuropein, and tyrosol exhibit potent antioxidant, anti-inflammatory, antimicrobial, and photoprotective effects. These compounds mitigate oxidative stress, prevent collagen degradation, modulate NF-κB and MAPK signaling, and promote cellular repair and regeneration. Skin health is increasingly recognized as crucial to overall well-being, driving interest in cosmeceuticals that combine cosmetic benefits with dermatological activity. This review examines the cosmeceutical and dermatological potential of OMWW, highlighting its incorporation into innovative topical formulations like oil-in-water nanoemulsions, liposomes, and microneedles that enhance skin penetration and bioavailability. Additionally, OMWW fractions have shown selective antiproliferative effects on melanoma cells, suggesting potential for skin cancer prevention. Valorization of OMWW through biorefinery processes aligns with circular-economy principles, converting agro-industrial waste into sustainable cosmeceutical ingredients. This approach not only meets consumer demand for natural, effective products, but also reduces the ecological footprint of olive oil production, offering a scalable, eco-friendly strategy for next-generation dermatological applications.

1. Introduction

As a multilayered organ, the skin serves essential physiological functions, including barrier integrity, thermoregulation, immune surveillance and photoprotection. Disorders affecting the skin, including cancer, infections, and inflammatory conditions, represent leading contributors to global disease burden, with substantial physical, psychological, and socioeconomic impact [1,2,3,4,5]. The public health significance of skin conditions has been recognized globally. Most recently, the 77th World Health Assembly (29 May 2024) emphasized the need to integrate dermatological care into universal health coverage systems due to the widespread and long-term consequences of untreated skin disorders [6]. Environmental and lifestyle factors, including diet, hydration, sleep, and stress management, significantly influence skin health, emphasizing the need for a holistic approach [7]. Fundamental skincare practices, such as cleansing, moisturizing, and the daily use of sunscreen, are essential to preserve and improve skin functions [8,9].

Epidemiological and preclinical studies indicate that populations in Mediterranean countries who traditionally adhere to the Mediterranean diet, characterized by a high intake of extra virgin olive oil (EVOO), exhibit a reduced risk of inflammation-related chronic diseases, including cancer [10]. Beyond its dietary use, EVOO has also been traditionally employed in Mediterranean cultures for cosmetic purposes, particularly in skincare, and, accordingly, mounting evidence supports its role in promoting skin health [11]. In line with the growing interest in olive-derived products, olive mill wastewater (OMWW), a byproduct of olive oil extraction, has attracted attention not only for its bioactive potential, but also due to its significant environmental burden. Although biodegradable, OMWW poses serious ecological risks: its high phenolic content and low pH contribute to phytotoxicity, while its lipid content promotes oxygen depletion, thereby disrupting aquatic ecosystems [12]. Notably, OMWW contains higher concentrations of phenolic compounds than olive oil itself, some of which have demonstrated relevance in topical pharmacology due to their anti-inflammatory effects, antimicrobial activity, wound-healing efficacy, antimelanoma potential, and photoprotective properties. Thus, the multifaceted role of OMWW phenolics in skin health and therapeutic skincare represents a valuable opportunity to repurpose an otherwise problematic waste product of olive oil extraction [13].

This review aims to explore the dermatological potential of OMWW by examining its bioactive composition, mechanisms of action, and preclinical evidence. It also discusses emerging formulation strategies for its application in cosmetic, dermatological and cosmeceutical products.

2. Methods

A literature review was conducted using the PubMed database to identify relevant studies on the dermatological applications of OMWW and other olive oil byproducts. The search was restricted to English-language articles published between 2000 and 2025. The following Medical Subject Headings (MeSH) terms and keywords were used in various combinations: “olive oil” OR “olive mill wastewater” OR “olive oil byproducts”; “phenolic compounds” OR “hydroxytyrosol” OR “oleuropein” OR “tyrosol”; “skin care” OR “cosmeceuticals” OR “topical formulations” OR “anti-aging” OR “photoprotection”; “nanocarriers” OR “nanoemulsions” OR “liposomes” OR “microneedling”; “hair growth” OR “dermal papilla cells” OR “VEGF” OR “IGF-1”;“anti-inflammatory” OR “NF-kB” OR “MAPK” OR “oxidative stress”; “skin cancer” OR “melanoma” OR “photocarcinogenesis”; “green chemistry/methods” OR “solvents/chemistry” OR “technology, pharmaceutical/methods” OR “sustainable development. Articles were selected based on their relevance to OMWW composition, biological effects, topical applications, and formulation strategies. Reference lists from key articles were also screened to identify additional studies.

3. Market Trends and Technical Advances

3.1. Leveraging Phytocompounds in Cosmeceutical Formulations

Cosmeceuticals occupy a unique position in skincare, bridging the gap between cosmetics and pharmaceuticals. These topical products are marketed as cosmetics but contain bioactive ingredients with functional properties suggestive of pharmacological activity. Typically aimed at improving skin appearance, cosmeceuticals also address underlying issues such as aging, pigmentation, and inflammation [14]. Despite their growing popularity, the term “cosmeceutical” is not officially recognized by regulatory bodies such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency. As a result, products marketed as cosmeceuticals are classified and therefore regulated either as cosmetics, drugs, or a combination of both, depending on their intended use and claims. Cosmetics are defined as articles intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, or altering appearance. Drugs, on the other hand, are articles intended for use in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body.

Regulatory distinctions include the following: 1. Products classified as cosmetics are subject to the regulations outlined in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the Fair Packaging and Labeling Act (FPLA). 2. Products classified as drugs must comply with drug regulations, including premarket approval requirements and good manufacturing practices. 3. Some products can be classified as both cosmetics and drugs if they have multiple uses or make both cosmetic and drug claims. Examples are antidandruff shampoos, acne treatment products that also serve as cleansers, antiperspirant deodorants and fluoride toothpaste.

This dual classification results in variability in the testing rigor, safety, and efficacy standards applied to cosmeceuticals. Some undergo pharmaceutical-grade evaluations, while others are subject to less stringent requirements.

The term “cosmeceutical” was first introduced by Dr. Albert Kligman in the 1980s [15], who proposed three criteria to define their efficacy:

• Penetration of Active Ingredients: The active compound must penetrate the stratum corneum in sufficient concentration to reach its target site within the skin.
• Known Mechanism of Action: The compound must have a clearly understood mechanism by which it achieves its effect, such as promoting collagen synthesis, inhibiting pigmentation, or reducing inflammation.
• Clinical efficacy: The product must demonstrate measurable results consistent with its claims, through well-designed studies.

The growth of the cosmeceuticals market has been significantly influenced by the Baby Boomer cohort, individuals born between 1946 and 1964, who exhibit a strong inclination towards maintaining dermal health and youthful aesthetics [16]. This demographic’s emphasis on anti-aging formulations targeting cutaneous concerns such as rhytides, dermal elasticity, and complexion radiance has positioned them as a crucial consumer segment in the cosmeceutical industry. Unlike preceding generations, Baby Boomers approach the aging process with a focus on sustained vitality and self-actualization, integrating cosmetic interventions with holistic wellness strategies [17]. This paradigm shift, combined with increasing global awareness of dermatological health, e-commerce expansion, and advancements in product formulations, has catalyzed rapid market growth. In 2022, the global cosmeceuticals market was valued at USD 56.08 billion and is projected to reach USD 128.54 billion by 2032, exhibiting a compound annual growth rate (CAGR) of 8.7% (Precedence Research, “Cosmeceuticals Market Size to Surpass USD 128.54 Bn by 2032”, March 2024). Skin care products dominate this market, accounting for USD 25.32 billion in 2022 and expected to reach USD 59.00 billion by 2032. Growth is particularly pronounced in the Asia Pacific region, with the market valued at USD 26.22 billion in 2023 and projected to reach USD 38.3 billion by 2030, growing at a 4.1% CAGR (Fortune Business Insights, “Cosmeceuticals Market Size, Share & Global Report 2032”, 2 December 2024). This growth is fueled by a rising middle class, increased disposable incomes, and heightened consumer awareness of cosmeceuticals’ benefits (Grand View Research, “Cosmeceutical Market Size & Share | Industry Report, 2030”, 1 October 2024). Influences like Western beauty standards and social media-driven skincare trends have further boosted demand.

The trend toward holistic wellness aligns with emerging evidence on the systemic benefits of plant-derived bioactive compounds, which have long been incorporated into cosmeceutical formulations for applications such as sun protection, hydration, anti-aging, and skin therapy. However, their effectiveness is often limited by poor skin penetration and instability, and nanotechnology-based delivery systems might improve both the stability and bioavailability of phytocompounds. Compounds like Aloe vera, curcumin, resveratrol, quercetin, vitamins C and E, genistein, and green tea catechins have successfully been delivered through formulations for use in creams, gels, and lotions targeting skin, lips, and hair [18].

3.2. Overview of Skin Care-Product Delivery Technologies

Modern skin care formulations increasingly rely on advanced delivery systems to enhance the effectiveness of active ingredients. Among these, emulsions typically consist of fine oil droplets dispersed in an aqueous base, resulting in a lightweight, easily absorbed formulation. They offer improved stability, sensory profiles, and efficacy, with rheological properties playing a key role in product optimization [19]. The performance of emulsion-based systems depends on multiple formulation parameters, including emulsion type, droplet size, emollients, and emulsifiers, all of which significantly impact the dermal and transdermal delivery of bioactive compounds [20,21]. These factors govern the interactions between the formulation vehicle, active agents, and skin layers, thereby determining the overall therapeutic efficacy [22].

Among the most promising advancements are nanoemulsions, which are fine O/W dispersions with nanoscale droplet sizes, typically ranging from 20 to 200 nanometers in diameter, and which enhance active ingredient delivery and skin penetration while potentially strengthening the skin barrier. Their small size allows these nanoscale emulsions to penetrate the skin’s barrier more effectively, enabling the encapsulation and delivery of a variety of active compounds, including hydrophilic and lipophilic molecules, to the target sites within the epidermis and dermis [23]. Similarly, liposomes are vesicles composed of phospholipid bilayers that can entrap both hydrophilic and lipophilic active ingredients. These nano-sized carriers can fuse with the stratum corneum, facilitating the transport of their cargo across the skin’s surface and into the deeper tissue layers [24]. Another innovative approach is microneedling, which involves the use of arrays of microscopic needles to create temporary, painless micropores in the stratum corneum. This technique allows for the enhanced permeation of topically applied active compounds, overcoming the skin’s natural barrier and enabling their delivery to the target sites within the epidermis and dermis [25].

Together, these advanced delivery systems hold the potential to overcome the key challenge in skincare: ensuring that active ingredients reach their target sites in sufficient concentrations to exert therapeutic or cosmetic effects.

4. Cosmeceutical and Dermatological Applications of Olive Oil Byproducts

4.1. Historical and Modern Applications of Olive-Based Skin Care and the Economic Valorization of Olive Oil Byproducts

In the holistic wellness scenario, evidence on the systemic benefits of olive-derived phytochemicals in human health is continuously emerging [26]. Historically, the use of olive oil and its byproducts in skincare dates back to ancient civilizations, including Egyptians, Greeks, and Romans. These cultures recognized olive oil’s moisturizing, cleansing, and protective properties, incorporating it into their daily skincare routines [27]. In ancient Greece, athletes applied olive oil before competition to enhance skin suppleness, prevent chafing, and protect against environmental exposure. It was also used in massages to alleviate muscle fatigue [28]. Interestingly, olive oil byproducts were also utilized, demonstrating an early understanding of the comprehensive benefits of olive processing [29]. The Greeks referred to the watery, bitter fluid that separates from olive oil during pressing as “amorge”, and they employed it for various purposes, including skincare. Later, the Romans adopted and expanded upon this knowledge, naming the substance “amurca”, which is well known for its anti-microbial activity [30]. A testament to the enduring legacy of olive-based skincare is the Aleppo soap from Syria, one of the oldest soaps in history. Made with olive oil and laurel oil, this traditional soap highlights the ancient yet timeless integration of olive derivatives into skincare practices [31].

Olive oil byproducts, once regarded solely as costly waste, are now being recognized for their potential to transform the economics of both agriculture and cosmetic production. The shift from waste disposal to resource valorization enables producers to reduce costs, generate revenue, and meet the growing demand for clean-label, sustainable skin care ingredients. Indeed, recent research has focused on the valorization of OMWW, due to its rich content of bioactive compounds, particularly phenolics [32,33], which account for up to 98% of the total phenols found in olive fruit [33,34].

OMWW and pomace are produced in massive quantities—up to 30 million m³ annually in the Mediterranean basin alone and, when untreated, they pose a significant economic burden and severe environmental risks due to their organic load, phenolic content, and low pH. However, the compounds that make OMWW an environmental concern also make it a potentially valuable resource for the cosmetic and pharmaceutical industries [29]. According to a recent work [35], treatment costs for OMWW can reach EUR 8–EUR 10 per cubic meter. Valorization through extraction, however, converts this liability into a resource, enabling the recovery of compounds like hydroxytyrosol and squalene with market prices ranging between EUR 500 and EUR 2000 per kilogram, depending on purity and formulation requirements. The exploitation of OMWW through biorefinery processes not only addresses environmental challenges but also enhances the economic viability of the olive oil industry. For instance, advanced extraction techniques such as ultrafiltration and resin-based methods have been shown to concentrate bioactive compounds like hydroxytyrosol to levels as high as 7204 mg/L [12,33]. While olive oil typically contains 50–800 mg/kg of total phenols, OMWW can contain up to 10,000 mg/L of these compounds, offering more potent antioxidant, anti-inflammatory, and antimicrobial properties compared to olive oil itself. These innovative approaches support the sustainable reuse of OMWW as a source of high-value compounds with potential applications in the biofuel, pharmaceutical, cosmetic, food, and agricultural sectors [32,33,36].

A scheme of the extraction of polyphenols from OMWW is depicted in Figure 1.

European-funded projects such as RE-WASTE, CYCLOLIVE, and OleaGREEN have demonstrated that integrating extraction technologies, particularly membrane filtration, ultrasound-assisted extraction, and supercritical CO₂, can generate high-quality phenolic fractions suitable for dermocosmetic formulations. These pilot studies have confirmed that small-scale modular units can be implemented at the mill level with modest capital investment and short payback periods [37,38,39]. For instance, the RE-WASTE pilot estimated that a polyphenol extraction unit could achieve cost recovery within three years when paired with biogas production from the residual biomass [39]. The CYCLOLIVE project also reported that upcycled polyphenols contributed to a 28% reduction in raw-material procurement costs for participating cosmetic manufacturers. Moreover, these ingredients support premium pricing due to their antioxidant efficacy and traceability, appealing to eco-conscious consumers willing to pay more for locally sourced, sustainable products [37,38].

From the perspective of olive producers, valorization offers a secondary revenue stream and mitigates disposal fees, particularly in regions where land application of OMWW is restricted or banned. In Italy and Spain, small and cooperative mills are already leveraging government incentives and Horizon Europe funding to integrate extraction systems with minimal disruption to traditional processes. In a broader economic context, this shift contributes to rural development, supports circular bioeconomies, and aligns with EU Green Deal objectives. The ability to repurpose agricultural waste into high-margin, bioactive ingredients marks a transition from linear to regenerative value chains—making olive byproduct valorization not just a sustainability strategy, but a competitive and scalable business model [35].

4.2. Characterization of Olive Oil and Olive Oil-Preparation Byproduct Composition: Applications in Dermatology

From the cosmeceutical point of view, olive oil and its derivatives, particularly those rich in polyphenols, have long been recognized for their multifaceted benefits [29]. The antioxidant, anti-inflammatory, and regenerative properties of olive polyphenols make them invaluable for addressing various skin concerns, from aging to environmental damage. These compounds, such as hydroxytyrosol and oleuropein, support skin health by combating oxidative stress, soothing inflammation, and promoting tissue repair. Indeed, it has been shown that the intake of EVOO is able to target crucial inflammatory pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and mitogen-activated protein kinase (MAPK), offering therapeutic benefits for managing inflammatory skin conditions [40]. Due to its high content in polyphenols, such as hydroxytyrosol and oleuropein, OMWW is increasingly recognized as a promising source of bioactive compounds with antioxidant, anti-inflammatory, and skin-protective properties, making it highly relevant for dermatological and cosmeceutical applications.

The composition of OMWW is diverse and can vary significantly depending on factors such as olive cultivar, maturation stage, and the technology used for oil extraction [41]. The potential applications in skincare of OMWW can be attributed to its unique chemical composition, particularly its high content of phenolic compounds. OMWW is predominantly composed of water (83–94%), organic matter (4–16%), and mineral salts (0.4–2.5%). The organic fraction includes sugars such as glucose, fructose, and mannitol; nitrogenous compounds like proteins and amino acids; various organic acids, including acetic, malic, and citric acids; as well as residual lipids derived from olive oil. Although present in smaller quantities, the minor components of OMWW are of particular interest due to their potent biological activities. Among these, phenolic compounds stand out as the most valuable for dermatological applications. More than 50 phenolics have been identified, including simple phenols (e.g., hydroxytyrosol and tyrosol), secoiridoids (such as oleuropein and its derivatives), flavonoids (like luteolin, apigenin, and their glycosides), and lignans (notably, pinoresinol and acetoxypinoresinol). These compounds, especially hydroxytyrosol and oleuropein, are known for their strong antioxidant, anti-inflammatory, and antimicrobial effects, making OMWW a promising ingredient for skincare formulations that might help soothe irritated or inflamed skin and be beneficial for sensitive or reactive skin types. OMWW contains low-molecular-weight phenolics, such as hydroxytyrosol and tyrosol, and higher-molecular-weight phenolics (600–5000 Da), including oleuropein, and verbascoside [42,43]. In addition, OMWW contains essential minerals, such as potassium, sodium, calcium, and magnesium, which support skin health, as well as trace amounts of vitamin E (tocopherols) and dietary fibers like mucilage and pectin, further enhancing its protective and restorative potential (

Table 1. Typical composition of olive mill wastewater (OMWW) by component category.

Component Category	Percentage	Reference
Water	83–94%	[41]
Organic Matter	4–16%
Mineral Salts	0.4–2.5%

). This rich composition has potential applications in skin care and dermatology (

Table 2. Composition of OMWW and biological relevance.

Component Category	Biological Role	Reference
Sugars	Energy supply and osmotic balance (glucose, fructose, and mannitol).	[44]
Nitrogenous Compounds	Cell repair and signaling (proteins and amino acids).	[45]
Organic Acids	pH regulation and antimicrobial action (acetic, malic, and citric acids).	[46]
Lipids	Skin barrier support (residual olive oil, essential fatty acids).	[46]
Phenolic Compounds	Antioxidant and anti-inflammatory activity (hydroxytyrosol, tyrosol, oleuropein, caffeic acid, and verbascoside).	[13,29]
Flavonoids	Anti-inflammatory and photoprotective effects (luteolin, apigenin, and glycosides)	[29,47]
Lignans	Antioxidant and anti-cancer properties (Pinoresinol and acetoxypinoresinol).	[46]
Vitamins	Skin protection and antioxidant defense (mainly vitamin E).	[46]
Minerals	Cellular hydration and function (potassium, sodium, calcium, and magnesium)	[45]
Dietary Fibers	Moisturizing and protective effects (mucilage and pectin)	[46]
Sugars	Energy supply and osmotic balance (glucose, fructose, and mannitol).	[44]

) [13], and also addresses a significant environmental challenge in olive oil-producing regions.

4.3. Anti-Aging Properties of OMWW

Recent scientific research has increasingly highlighted the skin benefits of olive oil derivatives as anti-aging products. Hydroxytyrosol and oleuropein, two prominent polyphenols found in olive leaves and OMWW, exhibit moderate inhibitory effects on elastase and collagenase, enzymes associated with skin aging [48]. These compounds, along with other antioxidants, play a crucial role in preventing photo-induced skin aging by neutralizing reactive oxygen species that contribute to wrinkles and atypical pigmentation [49]. Studies on OMWW extracts rich in hydroxytyrosol have demonstrated their ability to reduce oxidative damage to skin cells. High-molecular-weight phenolics present in these extracts demonstrate efficient scavenging activities against hydroxyl and peroxyl radicals [42]. Their antioxidant activity, alongside their anti-inflammatory action and their ability to support skin structure and barrier function, work synergistically to reduce signs of aging such as wrinkles, loss of elasticity, and dullness, helping to maintain healthier, more youthful-looking skin [50].

4.4. Photoprotective Properties of OMWW

By integrating OMWW polyphenols, skin care products can achieve superior sun protection. Studies reveal that OMWW fractions exert both antioxidant and pro-oxidant effects on UV-A-damaged keratinocytes, suggesting a dual mechanism of photoprotection [50]. Olive oil derivatives exhibit remarkable photoprotective properties, making them valuable additions to sunscreen formulations. Their ability to mitigate the damaging effects of UV radiation has been attributed primarily to phenolic compounds such as hydroxytyrosol and oleuropein. These bioactive molecules help counteract the harmful impact of both UV-A and UV-B rays, which are known to induce oxidative stress, inflammation, DNA damage, and an increased risk of skin cancer. Hydroxytyrosol and oleuropein exert their protective effects through multiple mechanisms. Their strong antioxidant capacity allows them to neutralize free radicals generated by UV exposure, preventing oxidative damage to cellular components [51]. Additionally, these compounds have demonstrated anti-inflammatory properties, reducing the release of pro-inflammatory cytokines that contribute to UV-induced erythema and long-term skin aging [52]. ROS, generated by UV exposure, pollution, and metabolic processes, can degrade collagen and elastin, accelerating the aging process. As stated above, oleuropein and hydroxytyrosol exhibit synergistic inhibitory effects on elastase and collagenase, enzymes associated with skin aging and extracellular matrix degradation [48,53]. In vitro studies using human keratinocytes have shown that OMWW significantly reduced reactive oxygen species (ROS) formation and protected against cellular damage. Accordingly, OMWW extracts demonstrate significant antioxidant properties, effectively scavenging free radicals and inhibiting LDL oxidation [42,54].

4.5. Anti-Inflammatory Effects and Pathway Modulation

The potential of OMWW in mitigating skin inflammation and oxidative stress relies mostly on its high polyphenol content. These bioactive compounds have been shown to modulate inflammatory signaling, notably by downregulating key pathways such as NF-kB and MAPK [13,55]. Elevated expression of phosphorylated NF-kB, extracellular Regulated Kinase 1 and 2 (ERK1/2), and p38 MAPK has been observed in several inflammatory skin diseases, including eczema and psoriasis [56]. Those signaling molecules drive the expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8, enzymes like inducible nitric oxide synthase (iNOS) and cyclooxygenase- 2 (COX-2) and increase oxidative stress and apoptosis in the local tissue [56,57]. Keratinocytes and resident immune cells are central to this process, and their dysregulation contributes to lesion formation and disease progression [58,59]. Several anti-psoriatic therapies, including TNF-α blockers and glucocorticoids, reduce active NF-kB levels, while novel therapeutics targeting NF-kB signaling are being developed for chronic inflammatory skin disorders [59].

A work showed that OMWW extract effectively reduced IL-8 release in human keratinocytes (HaCaT cells) after TNF-α stimulation, suggesting strong anti-inflammatory properties comparable to that of hydrocortisone. Also, OMWW significantly decreased hydrogen peroxide-induced ROS formation in HaCaT cells, displaying an antioxidative effect superior to that of 100 µM ascorbic acid, indicating a robust ability to protect skin cells from oxidative stress. The observed time-dependent effect also allowed for the assessment of both immediate and prolonged effects of the extract, potentially offering insights into its ability to mitigate inflammation over time [60].

OMWW-derived formulations demonstrated topical anti-inflammatory efficacy in both in vitro and in vivo models, reducing IL-1α, IL-8, iNOS, and COX-2 expression [61].

These findings support the potential use of OMWW-derived compounds in dermatology and dermo-cosmetic preparations for skin health and protection. Besides this, their properties make them attractive candidates for nutraceutical interventions to ameliorate systemic inflammation in aging subjects, potentially addressing the low-grade inflammatory state known as “inflammaging” [62,63,64].

4.6. Antimicrobial Properties and Skin-Barrier Restorative Properties of OMWW

Beyond their antioxidant and anti-inflammatory functions, these phenolics also exhibit antimicrobial activity against common skin pathogens, including Staphylococcus aureus and Propionibacterium acnes, therefore offering potential benefits for managing acne-prone or blemished skin [53]. In addition, OMWW contributes to the reinforcement of the skin’s barrier function. Studies have shown that its polyphenols support keratinocyte repair and migration, essential for maintaining the integrity of the epidermis and promoting skin resilience [50].

4.7. Skin Cancer Prevention and Selective Antiproliferative Effects

Olive-derived extracts, including OMWW and those from olive leaves (OLE), have shown considerable promise in the prevention and treatment of skin cancers, particularly melanoma, in both in vitro and in vivo models [65].

These extracts exhibit multifaceted mechanisms of action, combining antioxidant, anti-inflammatory, and modulatory activity on several signaling pathways. OMWW extracts have demonstrated potential in selectively inhibiting A375 melanoma cell proliferation while enhancing the growth of normal human epidermal keratinocytes. The selective inhibition of melanoma cell proliferation while sparing normal human epidermal keratinocytes highlights their safety and specificity [60]. Similarly, OLE has been shown to suppress melanoma cell proliferation, invasion, and epithelial-to-mesenchymal transition [66]. The anti-cancer properties of olive-derived extracts are attributed to their ability to induce cell cycle arrest and apoptosis [67], to modulate the MAPK, phosphatidylinositol 3-kinase (PI3K), and the signal transducer and activator of transcription 3 (STAT3) signaling pathways [60,66], alongside their antioxidant and anti-inflammatory effects [53,60]. OMWW has also been shown to suppress the C-X-C chemokine receptor type 4 (CXCR4)-mediated signaling in lung cancer, thereby interfering with the formation of metastasis [68].

Studies have noted the low toxicity of phenolic compounds enriched in OMWW on normal cells. OMWW is characterized by a high content of oleuropein [69], which demonstrates potent anti-melanoma activity by inducing apoptosis and inhibiting the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway in B-rapidly accelerated fibrosarcoma (BRAF)-mutated melanoma cells. At 250 µM, oleuropein significantly reduces melanoma cell viability and enhances the cytotoxicity of chemotherapeutic agents. Importantly, it selectively targets melanoma cells while sparing normal fibroblasts, likely due to differential uptake via glucose transporters 1 and 3 (GLUT1/3), which are overexpressed in cancer cells. This selectivity highlights oleuropein’s promise as a non-toxic therapy across different pathologies, including cancer [70]. This safety profile, combined with the extracts’ antimicrobial activity [69] and ability to reduce ROS formation [71], suggests significant potential for various skin-related applications, particularly in the realm of skin cancer prevention.

This dual action, enhancing efficacy while reducing toxicity, has also been observed in breast cancer models treated with OMWW-derived extracts [72]. Anti-inflammatory and anti-angiogenic properties of OMWW extracts have been documented in prostate cancer models [73]. The chemopreventive potential of OMWW extracts has been observed, due to their ability to inhibit colon cancer cell growth in vitro and in vivo [74]. Polyphenol-rich OMWW extracts may potentiate the effects of chemotherapy while minimizing off-target damage [75], aligning with the broader evidence supporting olive compounds as key nutraceuticals in disease prevention and interception [76].

4.8. Hair Health and Follicular Stimulation by OMWW

Scalp hair growth is a complex biological process governed by the intricate interplay of structural components and cyclical phases. The growth process is regulated by hair follicles, specialized structures composed of both epithelial and dermal components. The epithelial component includes protective sheaths surrounding the hair shaft, while the dermal component, particularly the dermal papilla at the follicle’s base, plays a pivotal role in regulating hair growth. Human follicle dermal papilla cells (HFDPCs) release growth factors such as insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF), which stimulate cell proliferation, maintaining the active growth phase [77]. Human scalp hair provides protection against harmful ultraviolet (UV) radiation, shielding the scalp from sunburn and minimizing the risk of long-term UV damage. Additionally, it helps regulate temperature by offering insulation, reducing heat loss in colder conditions while minimizing direct heat exposure in warmer climates [78]. Hair follicles are also connected to nerve endings, giving scalp hair a sensory role [79]. This sensitivity allows individuals to detect subtle external stimuli, including the presence of small particles or even insects on the head. Beyond these physical functions, scalp hair plays a prominent role in social and cultural contexts. Hairstyles and hair care practices are powerful expressions of identity, attractiveness, and social status, often carrying deep personal or cultural meaning. Issues like thinning or loss can lead to significant emotional distress and affect social interactions. Hair growth follows a cyclical pattern divided into three main phases: anagen, catagen, and telogen, with some researchers also recognizing exogen (shedding) as a distinct phase [80]. The anagen phase is the active growth stage, the catagen phase is a brief transitional period, during which the hair follicle shrinks and detaches from the dermal papilla, signaling the end of active growth, and, finally, the telogen phase is a resting stage where old hair is shed to make way for new growth. Human hair follicles cycle asynchronously, ensuring that individual follicles undergo these phases independently, preventing uniform shedding or growth across the scalp [81]. However, disruptions to this cycle can lead to hair thinning or loss [80,82].

Hormonal imbalances, such as those caused by polycystic ovary syndrome (PCOS) or thyroid disorders can interfere with follicle function [53]. Nutritional deficiencies, particularly in iron, zinc, or biotin, also impede healthy hair growth [83]. Environmental factors, including UV radiation and pollution, contribute to oxidative stress, damaging hair follicles and accelerating hair aging [84]. Also, dihydrotestosterone (DHT) plays a significant role in the pathogenesis of androgenetic alopecia (AGA), the most common form of hair loss. DHT is a potent androgen derived from testosterone through the action of the 5α-reductase enzyme. A study evaluated the usefulness of DHT levels in diagnosing AGA and found that, while DHT is crucial in AGA pathogenesis, serum DHT levels alone may not be a reliable diagnostic marker. The authors concluded that the most important factors in AGA development appear to be the genetically determined sensitivity of hair follicles to DHT and their varied reactions to androgen concentrations [85]. DHT binding to androgen receptors in susceptible hair follicles leads to follicular miniaturization and eventual hair loss [86].

A study carried out by Lisa-Marie Sittek’s group [87] explored the potential of OMWW extract as a promising ingredient for hair care and hair growth enhancement. The findings revealed that OMWW extract significantly enhanced the proliferation of HFDPCs and increased the secretion of IGF-1 and VEGF, indicating its potential to promote hair growth. Furthermore, the OMWW extract exhibited a concentration-dependent ability to reduce ROS levels, with the highest dilution (1:250) leading to a remarkable 60.76% reduction in free radicals. Since DHT has been shown to increase ROS production [87] and reduce IGF-1 expression, leading to impaired hair follicle proliferation and suppressed hair regrowth [88], OMWW may offer therapeutic benefits in AGA by counteracting these effects.

Table 3. Biological effects of OMWW: summary of in vitro and in vivo studies.

Type of Study	Cells/Tissue	Effect
In vitro	Keratinocyte [60]	Antibacterial; antioxidant (decreased ROS); anti-inflammatory (decreased IL-8); photoprotection.
	Human follicle dermal papilla [87]	Increased proliferation and IGF-1; decreased ROS; antioxidant protection.
	HaCaT cells (keratinocytes) [60]	Decreased IL-8 after TNF-α; anti-inflammatory effect comparable to hydrocortisone.
	Normal human epidermal keratinocytes [50]	Increased growth and migration; antioxidant activity; improved barrier function.
	A375 melanoma cells [60]	Selective cytotoxicity to melanoma cells; no toxicity for normal cells.
	HFDPCs (human follicle dermal papilla cells) [87]	Increased IGF-1, VEGF and proliferation; antioxidant action.
In vivo	Human skin (clinical) [44]	Increased hydration and elasticity; decreased erythema index.

provides an overview of the in vitro and in vivo effects of OMWW on cells and tissue, while

Table 4. Dermatological Roles of OMWW and Its Bioactive Components and potential formulations for topical use.

Bioactivity	Experimental Model	Intervention	Outcome Parameters	Key Findings	References
Antioxidant Activity	HaCaT keratinocytes	OMWW extract (phenol-enriched); 100 µM ascorbic acid control	ROS levels	Decreased ROS > 60%; superior to ascorbic acid	[60]
Anti-inflammatory Effects	HaCaT keratinocytes	OMWW extract; TNF-α stimulation	IL-8, iNOS, COX-2	Decreased IL-8 expression, comparable to hydrocortisone	[60,61]
Photoprotection	Human keratinocytes	OMWW polyphenols (hydroxytyrosol, oleuropein); UVA/UVB exposure	Inflammatory cytokines, ROS, collagen	Decreased cytokines and ROS; preserved collagen	[50,51]
Antimicrobial Activity	In vitro; S. aureus, P. acnes, C. albicans	OMWW extract (MIC 50–200 µg/mL)	Pathogen viability	Inhibited bacterial/fungal growth	[53,69]
Skin Barrier Enhancement	Human keratinocytes	OMWW extract	Cell migration, hydration markers	Increased keratinocyte migration and hydration	[50]
Anti-aging Effects	Fibroblasts	OMWW extract; 0.1–1 mM	Elastase, collagenase activity, ROS	Decreased collagenase/elastase activity; increased collagen matrix	[48,53]
Hair Growth Promotion	HFDPC (dermal papilla cells)	OMWW extract (1:250 dilution)	IGF-1, VEGF, ROS	Increased IGF-1/VEGF; decreased ROS by 60%; increased proliferation	[87]
Skin Cancer Prevention	A375 melanoma cells	OMWW extract, oleuropein (250 μM)	Apoptosis, viability	Decreased melanoma viability; increased apoptosis; spared normal keratinocytes	[60,70]
ROS Scavenging	Multiple (HaCaT, HFDPC)	OMWW extract	ROS levels	Decreased ROS in both keratinocytes and DPCs	[60,87]
Wound Healing Support	Human fibroblasts, in vivo mouse model	OMWW extract	Fibroblast proliferation, collagen synthesis	Increased fibroblast activity, accelerated tissue regeneration	[44]

provides an overview of the key bioactive properties of OMWW and its constituent compounds, highlighting their mechanisms of action and potential dermatological applications and cosmeceutical formulations. Figure 2 depicts the functions of OMWW-derived polyphenols at the molecular level and their potential effects on the skin.

4.9. Formulations for the Delivery of OMWW Compounds

While the stratum corneum is essential for maintaining skin integrity, this protective mechanism presents a significant challenge for the delivery of active ingredients in skin care [89,90]. To address this, the cosmetic industry has developed innovative formulations and technologies, such as nanoemulsions, liposomes, and microneedling, which can selectively overcome the skin’s barrier function and enable the targeted delivery of active compounds to deeper skin layers [91,92,93,94]. Among these, oil-in-water (O/W) emulsions are particularly valued for their ability to solubilize and deliver natural compounds with antimicrobial and anti-inflammatory activity that are otherwise poorly soluble [95]. The integration of OMWW into O/W emulsions presents a promising approach for addressing oxidative and inflammatory skin stress. These formulations can potentially harness the synergistic effects of OMWW’s diverse bioactive compounds, offering a multifaceted approach to skin health [95]. In vivo studies have shown promising results, with a sugar- and mineral-enriched fraction from OMWW improving skin hydration without adverse effects [44].

These findings highlight the potential of OMWW-based formulations to offer a comprehensive approach to skin health, addressing multiple concerns simultaneously, including hydration, photoprotection, anti-aging, and, potentially, even skin cancer prevention.

4.10. Regulatory Landscape and Research Initiatives on OMWW in the EU

Despite the significant environmental burden posed by olive mill wastewater, there is currently no binding EU-wide legislation specifically addressing its recycling or valorization [35,96,97]. While overarching directives such as the Waste Framework Directive (2008/98/EC) and the Water Framework Directive (2000/60/EC) (European Commission, 2008) provide general environmental protection, they do not offer clear or harmonized guidance tailored to OMWW [98]. This absence of specific regulation has led to considerable variation in how member states approach OMWW disposal and reuse, with policies often reflecting regional priorities, administrative capacity, and the scale of local olive oil production [97].

To compensate for this legislative gap, numerous EU-funded projects have emerged over the past two decades. Among the earliest was the RE-WASTE project (2009–2012), which demonstrated that OMWW could be efficiently treated to extract high-value compounds like polyphenols and biogas. More recently, the CYCLOLIVE project (2023–2026) has extended this work by focusing on the conversion of OMWW solids into biochar and water-absorbent biopolymers for agricultural applications, alongside enhanced wetland-based treatment systems to improve water purification. Similar small-scale solutions, including hybrid constructed wetlands, have been used effectively in decentralized OMWW treatment pilot projects [99]. Other initiatives, such as TIRSAV+, and PROSODOL, have promoted the composting of OMWW into organic fertilizers and examined the impact of OMWW on soil quality, advocating for regulatory models that support land restoration and responsible waste management [100]. The Rhodolive project has further demonstrated the potential for OMWW to be converted into biodiesel and animal feed through microbial fermentation [101].

Recent studies have further demonstrated the potential for OMWW valorization through the recovery of polyphenols for animal feed, biogas production, and the development of biochar and biopolymers, all of which align with circular-economy principles [35,102]. Advances in digital monitoring and IoT-based solutions are enabling more efficient and sustainable management practices [103]. These scientific developments underscore the importance of integrating innovative technologies with policy reforms to achieve effective, large-scale OMWW valorization.

Despite these technological advances, regulatory practices remain inconsistent across the EU. In Italy, OMWW governance is largely regional, with some jurisdictions permitting agricultural reuse under strict monitoring and others classifying OMWW as hazardous waste requiring special disposal [97]. Spain, the EU’s largest olive oil producer, supports the use of OMWW in composting and irrigation through regional policies but lacks cohesive national legislation. Greece and Portugal have implemented local restrictions and pilot programs to mitigate environmental risks, but enforcement and infrastructure vary widely. France, though a smaller producer, has focused on integrating OMWW into organic soil amendments through research-based strategies [104]. The lack of standardized national policies continues to hinder the large-scale adoption of sustainable OMWW management and creates uncertainty for producers and technology developers [97].

Economically, OMWW valorization is gaining traction, as studies indicate that transforming OMWW into compost or extracting bioactive compounds can offset disposal costs and create marketable products [96]. However, economic feasibility remains challenging for small-scale producers, who often face high capital costs for treatment technologies and lack uniform subsidies or incentives [97].

To address these regulatory and economic challenges, researchers have proposed the development of a common EU framework that would establish standardized thresholds for key parameters such as polyphenol concentration, electrical conductivity, and pH, and provide a clear legal pathway for OMWW reuse in agriculture, energy, and cosmeceuticals [97]. Such a framework would align with the EU Green Deal and circular-economy strategies, supporting sustainability, innovation, and equitable growth across olive-producing regions. It would also reduce legal uncertainty, attract investment in valorization technologies, and ensure more consistent environmental monitoring and enforcement throughout the EU [97].

4.11. Green Extraction Techniques for OMWW Valorization

Extracting bioactive compounds from OMWW requires techniques that can preserve the functional integrity of phenolics while meeting safety, sustainability, and regulatory standards. Green extraction methods have gained prominence, as they reduce or eliminate the use of toxic solvents, operate under milder conditions, and offer better compatibility with clean-label and eco-certified formulations. Compared to conventional methods, these approaches are designed to maximize yield, minimize energy and solvent consumption, and facilitate scalability for industrial use. Each technique offers distinct benefits in terms of selectivity, scalability, and suitability for extracting specific classes of bioactive molecules relevant to cosmeceutical applications [105].

Supercritical CO₂ extraction is widely recognized for its precision and non-toxicity. Operating under elevated pressures and moderate temperatures, this technique efficiently isolates lipophilic compounds such as squalene and antioxidant-rich phenolics without leaving harmful residues. Because CO₂ is recyclable and chemically inert, it is ideal for producing high-purity extracts compatible with cosmetic formulations [106].

Ultrasound-Assisted Extraction (UAE) employs acoustic energy to create cavitation bubbles that rupture plant cell walls, facilitating the release of intracellular compounds such as hydroxytyrosol, tyrosol, and other phenolic antioxidants. UAE is particularly valued for its mild operational conditions, typically below 50 °C, which help preserve the structural integrity and bioactivity of sensitive molecules. Its low energy consumption, reduced solvent requirements, and short extraction times make it an attractive option for sustainable, small-scale cosmetic ingredient production [107].

Microwave-Assisted Extraction (MAE), by contrast, relies on rapid volumetric heating caused by microwave radiation to disrupt cell structures and accelerate mass transfer. This method is highly efficient, often completing extractions within minutes, and is well-suited for processing large volumes of OMWW or pomace. However, careful optimization is required to avoid thermal degradation of thermolabile compounds. MAE has shown strong performance in recovering phenolics and flavonoids, and can be tuned to selectively enrich fractions based on polarity and moisture content [108].

Pressurized liquid extraction (PLE) uses elevated pressure and temperature to improve solvent penetration and solute diffusion. This technique allows efficient extraction of a wide range of polar and semi-polar compounds, including hydroxytyrosol and other phenolic antioxidants, while using significantly less solvent than conventional methods [109].

Deep eutectic solvents (DESs) are gaining attention as customizable, biodegradable alternatives to traditional solvents. Formed from natural components like sugars, organic acids, or amino acids, DESs can be tailored to solubilize specific compounds in OMWW. Their tunability and low toxicity make them promising for selective extraction of bioactive ingredients intended for dermocosmetic use [110].

Microwave-assisted extraction (MAE) employs electromagnetic radiation to rapidly heat the solvent and plant matrix, facilitating the breakdown of cell structures and releasing heat-sensitive phytochemicals. This method offers high efficiency and energy savings, and is particularly well-suited for recovering compounds with antioxidant and anti-inflammatory potential [111].

Membrane-based purification techniques, including ultrafiltration, nanofiltration, and reverse osmosis, play a particularly important role in the upcycling of OMWW for cosmetic applications. These processes operate without the use of additional chemicals, making them ideal for producers who prioritize sustainability and clean-label formulations. Membranes selectively separate phenolic compounds and other low-molecular-weight bioactives from larger organic residues, resulting in highly concentrated, microbiologically stable extracts. The absence of harsh solvents also helps preserve the integrity of antioxidant molecules, ensuring that the recovered fractions retain their efficacy in topical skin care products. Importantly, membrane systems can be modular and energy-efficient, allowing for integration into small-scale or eco-certified production facilities without compromising product quality or environmental performance [112].

Complementing these are recent advancements in bio-based solvent extraction, which offer additional flexibility for targeting specific phenolic profiles. A recent study evaluated the use of ethyl acetate (EA), 2-methyltetrahydrofuran (2-MeTHF) and cyclopentyl methyl ether (CPME) for recovering polyphenols from different OMWW streams. While EA demonstrated the highest extraction efficiency for total polyphenols (up to 421 mg GAE/L), 2-MeTHF was most effective for flavonoids, and CPME showed superior solvent recyclability, up to 55% recovery, making it particularly appealing from a sustainability standpoint [113].

4.12. Sustainability and Economic Value Addition

Eco-friendly branding in the cosmetics sector relies not only on sourcing sustainable ingredients, but also on transparent storytelling that connects the origin and benefits of these ingredients with consumer values. Products made with upcycled olive byproducts such as OMWW appeal to increasingly environmentally conscious consumers who seek clean-label, traceable, and ethically sourced alternatives to conventional formulations. As outlined by Yang and Hamid [114], consumers are more likely to purchase skin care products that align with values such as reducing their carbon footprint, supporting biodiversity, and minimizing waste, especially when those products are backed by credible claims and scientific validation.

One effective approach is to highlight the dual value of upcycled ingredients: their functional efficacy and their reduced environmental impact. For example, it has been demonstrated that OMWW-derived polyphenols not only reduced the environmental burden of olive production but also improved skin hydration and barrier function in clinical testing, providing a powerful basis for brand differentiation [115]. Labels such as “zero waste,” “upcycled,” or “byproduct valorized” can reinforce this message when supported by data on ingredient performance and lifecycle sustainability.

Visual identity, packaging choices (e.g., recyclable or refillable materials), and carbon labeling can further support eco-branding. Social proof, such as partnerships with local mills, certifications, and endorsements from eco-conscious influencers, can also enhance trust. In a market where consumers increasingly expect products to reflect their values, combining technical performance with authentic sustainability narratives is key to gaining both credibility and loyalty. At the production level, the economic case for upcycling OMWW is clear, but the infrastructure to realize it is often lacking, especially among small and medium-sized olive mills. Policy tools such as tax credits, grants, or innovation vouchers could accelerate the adoption of green extraction technologies by making them more accessible and cost-effective. This shift would not only reduce the environmental impact of olive farming but also open up new revenue streams for producers who might otherwise treat OMWW as waste.

5. Future Perspectives

The promising results obtained from OMWW-based formulations open several avenues for future research and development within the cosmeceutical sector. OMWW extracts, rich in phenolic compounds such as hydroxytyrosol, oleuropein and verbascoside, exhibit significant antioxidant, anti-inflammatory, and regenerative activities that can be harnessed for skin health applications. This will be essential for consumer confidence, and clinical validation. Mechanistic studies at the molecular and cellular levels are warranted to better elucidate how OMWW components interact with skin cells, particularly keratinocytes, fibroblasts, and immune mediators. Transcriptomic and proteomic analyses may offer insights into the modulation of skin aging pathways, barrier function, and inflammatory signaling by OMWW-derived actives. From a translational perspective, clinical trials assessing the efficacy and tolerability of OMWW-enriched formulations in humans are a next step. Pilot studies focused on conditions such as atopic dermatitis, photoaging, or sensitive skin could help position OMWW-based products within niche dermatological markets. Expanded research into the long-term safety, dermal absorption, and functional outcomes of OMWW-derived actives would help solidify their place in the cosmetic formulary and support claims that go beyond novelty into proven benefit. Furthermore, there is an opportunity to explore synergistic combinations of OMWW with other natural actives, such as ceramides, niacinamide, or botanical oils, to enhance barrier restoration, hydration, and anti-aging properties. Advanced delivery systems, including nanocarriers or encapsulation techniques, could further optimize skin penetration and stability of polyphenolic compounds. A primary future direction involves the standardization of OMWW-extract composition. Given the variability in phenolic content due to olive cultivar, milling process, and extraction method, further studies are needed to establish reproducible extraction protocols that ensure consistent bioactive profiles in final formulations. Also, future research should prioritize the optimization of extraction and purification techniques to maximize the yield of bioactive compounds, such as hydroxytyrosol, tyroso, verbascoside and oleuropein, while maintaining their biological activity. Advances in nanotechnology and delivery systems could further enhance the bioavailability and skin penetration of these potent polyphenols, holding promise for applications in anti-aging creams, regenerative serums, hair care and photoprotective lotions. The synergy between nanoemulsions and microneedling might maximize the therapeutic potential of OMWW.

Greater collaboration between sectors could help bridge scientific promises and market execution. Research into extraction techniques and compound efficacy often operates in isolation from regulatory conversations or commercial formulation. By fostering dialogue between cosmetic chemists, agronomists, and policymakers, the industry could more effectively align safety data, innovation goals, and consumer protection. From a marketing standpoint, OMWW-based ingredients offer a unique opportunity to connect sustainability with functionality. But this potential will only be realized if consumers are brought into the conversation with transparent, evidence-based messaging. Labels such as “upcycled,” “waste-derived,” or “Mediterranean origin” must be backed by accessible narratives about safety, efficacy, and environmental benefit. This is especially important in a cosmetic landscape increasingly defined by clean-label expectations and brand trust.

A greater emphasis on biorefinery processes may also support the sustainable valorization of OMWW, aligning with circular-economy principles by transforming an environmental pollutant into a valuable dermatological resource. Collaborative efforts between industry, academia, and regulatory bodies will be crucial to standardize product formulations, ensuring quality, safety, and efficacy. These initiatives could position OMWW-derived products as a flagship example of sustainable innovation in modern dermatology.

6. Discussion and Conclusions

Today, the cosmetic industry is increasingly incorporating olive-derived bioactives from byproducts like OMWW, pomace, and leaves [116]. These byproducts contain valuable compounds such as poly-unsaturated fatty acids (PUFA), polyphenols, tocopherols, and vitamins, which offer antioxidant, anti-aging, and antimicrobial properties [116]. Figure 3 summarizes the extraction process of polyphenols from OMWW, their biological activities and their potential use in dermatology and cosmetology.

Besides this, extracts from olive byproducts show promise in cancer prevention and cardioprotection, highlighting their potential in modern healthcare applications [29]. Building on this foundation, products incorporating active compounds from OMWW, a by-product of olive oil production, exemplify the next level of innovation. OMWW contains even higher concentrations of phenolic compounds than olive oil itself, offering superior antioxidant and anti-inflammatory properties. These bioactive components align with Kligman’s last two principles by demonstrating clear mechanisms of action and measurable outcomes in scientific studies. Many polyphenols in OMWW, such as hydroxytyrosol and tyrosol, are relatively small molecules, which may enhance their ability to penetrate the skin, aligning with Kligman’s first principle.