Efficacy and Safety of Natural Versus Conventional Toothpastes and Mouthwashes in Gingivitis Management: A Systematic Review

Abstract

Gingivitis is a common and reversible inflammatory condition caused by dental plaque accumulation, which, if left untreated, can progress to periodontitis. Conventional oral care products like chlorhexidine (CHX) and fluoride are effective in plaque control but are often associated with adverse effects such as dental staining and mucosal irritation. This systematic review aimed to compare the efficacy and safety of natural versus conventional toothpastes and mouthwashes in managing plaque-induced gingivitis. The review followed PRISMA guidelines and was registered in PROSPERO (No. 1008296). A systematic search was conducted across PubMed, Web of Science, and Scopus for English-language clinical studies published between 2015 and 2025. Eligible studies included randomized controlled trials and clinical trials on human subjects with plaque-induced gingivitis. Exclusion criteria were studies on animals, in vitro experiments, review articles, and studies lacking control groups. Data extracted included intervention type, sample characteristics, clinical indices (PI, GI, SBI), inflammatory biomarkers, adverse events, and patient adherence. A narrative synthesis was conducted due to study heterogeneity. Fifteen studies were included. Natural products such as neem, green tea, aloe vera, and propolis demonstrated comparable effectiveness to CHX and fluoride in reducing gingival inflammation and plaque indices, with a lower incidence of side effects. In particular, natural formulations showed superior tolerability and better patient compliance, especially in long-term use. However, variability in concentration and the formulation of natural products limits their clinical standardization. In conclusion, natural oral care products appear to be effective and better-tolerated alternatives to conventional agents in managing gingivitis. Nonetheless, further long-term, standardized clinical trials are needed to confirm their efficacy and define optimal formulations.

1. Introduction

Gingivitis is a prevalent early-stage periodontal disease that affects a significant portion of the global population, with prevalence rates reaching up to 90% among adults [1].

This condition is characterized by reversible inflammation of the gingival tissues, primarily due to bacterial plaque accumulation along the gum line. Common symptoms include gum redness, swelling, bleeding during brushing, and, in some cases, bad breath. If left untreated, gingivitis can progress to periodontitis, a more severe condition that leads to the destruction of tooth-supporting structures, increased mobility, and potential tooth loss. Emerging research has established a connection between gingiva1 inflammation and systemic health, linking periodontal diseases to conditions such as cardiovascular disease, diabetes, respiratory disorders, and pregnancy complications. This underscores the importance of proper oral hygiene in maintaining overall health and preventing systemic complications [2].

Managing gingivitis involves controlling bacterial plaque through routine oral hygiene practices, including tooth brushing and interdental cleaning with floss or interdental brushes [3,4,5]. However, mechanical cleaning alone may not suffice to maintain optimal oral health, leading to the widespread use of toothpastes and mouthwashes with active ingredients aimed at reducing inflammation and bacterial load [6,7].

Traditional toothpastes and mouthwashes incorporate synthetic agents designed to control bacterial growth, reduce inflammation, and prevent tartar buildup. Chlorhexidine (CHX) is widely recognized as the gold standard for oral antiseptics due to its potent antibacterial properties [8,9,10,11]. However, prolonged use is associated with side effects, including tooth discoloration, taste disturbances, and mucosal irritation [12]. Sodium fluoride, primarily known for its anti-cavity effects, also aids in gingivitis management by strengthening enamel and limiting bacterial colonization [13,14]. Triclosan, an antibacterial agent with anti-inflammatory properties, has been combined with copolymers to enhance its efficacy, although concerns regarding its environmental and health impact have led to regulatory scrutiny [7,15]. Additional agents such as pyrophosphates and zinc compounds help prevent plaque accumulation and tartar formation, while many mouthwashes contain essential oils that provide a refreshing effect along with mild antibacterial action [16,17,18].

Interest in natural oral care products has grown due to increasing awareness of potential side effects associated with synthetic ingredients [19]. Herbal and plant-based formulations offer an alternative approach by leveraging natural antibacterial, anti-inflammatory, and wound-healing properties [20,21,22]. Although their efficacy varies, numerous studies indicate that specific plant-based compounds contribute to plaque reduction and inflammation control [23,24,25]. Since bacterial plaque accumulation is the primary cause of gingivitis, several natural ingredients have demonstrated effective antibacterial activity [26,27]. For instance, green tea contains catechins such as epigallocatechin gallate (EGCG), which possess strong antimicrobial and antioxidant effects, inhibiting bacteria such as Porphyromonas gingivalis. Propolis, a resinous substance produced by bees, has broad-spectrum antibacterial properties that help reduce bacterial proliferation [28,29].

Additionally, xylitol interferes with bacterial metabolism, limiting the growth of harmful oral bacteria, while tea tree oil has exhibited antimicrobial efficacy, contributing to inflammation control. Beyond bacterial control, managing inflammation is critical in gingivitis treatment. Several plant-derived ingredients possess bioactive compounds that modulate the inflammatory response and promote tissue healing. Aloe vera is well known for its soothing, anti-inflammatory, and wound-healing capabilities. Chamomile, which contains flavonoids and terpenoids, helps alleviate gingival irritation and supports tissue regeneration. Curcumin, the active component of turmeric, has demonstrated anti-inflammatory effects comparable to certain nonsteroidal anti-inflammatory drugs (NSAIDs) [30]. Clove oil, rich in eugenol, provides analgesic and anti-inflammatory benefits [31].

One of the advantages of natural oral care products is their potential to promote gingival healing and regeneration [32,33]. Propolis enhances cellular repair and accelerates wound healing, while aloe vera contributes to tissue hydration and regeneration. Additionally, Centella asiatica has been found to stimulate collagen production, aiding in tissue recovery [34].

A primary benefit of natural toothpastes and mouthwashes is their greater tolerability, particularly for individuals with sensitive oral mucosa or allergies to synthetic chemicals. Unlike conventional products, they do not contain CHX, which is known to cause staining, taste alterations, and mucosal irritation with prolonged use [12]. Many natural formulations are also free from Sodium Lauryl Sulfate (SLS), a foaming agent that may contribute to oral irritation [35]. From an environmental perspective, natural products often contain biodegradable ingredients and are free from microplastics, reducing ecological impact [36].

Despite their advantages, natural oral care products present some challenges. Their effectiveness depends on the concentration and bioavailability of active compounds, requiring careful formulation to ensure optimal results [37,38]. While many studies suggest promising outcomes, further long-term clinical trials are needed to establish their definitive role in gingivitis management [39]. In cases of advanced gingivitis, natural products should complement, rather than replace, professional dental treatments. This systematic review aims to bridge this gap by evaluating the efficacy and safety of plant-based versus conventional oral hygiene products for plaque-induced gingivitis [40,41,42].

2. Materials and Methods

The increasing popularity of natural oral care products necessitates a scientific assessment of their efficacy and safety in gingivitis management. This study aims to compare plant based toothpastes and mouthwashes with conventional formulations, evaluating their mechanisms of action, benefits, and limitations.

By providing an evidence-based overview, this study seeks to assist oral health professionals in making informed therapeutic recommendations. Additionally, potential side effects and the long term implications of using both conventional and natural products will be examined, contributing to a more comprehensive understanding of gingivitis treatment options.

2.1. Processing Searches

We looked through databases like Scopus, Web of Science (WaS), and PubMed using the keywords “gingivitis AND natural” to locate studies that addressed this subject.

The databases PubMed, Scopus, and Web of Science were searched in March 2025 using full search strings such as (‘gingivitis’ AND ‘natural’) AND (‘toothpaste’ OR ‘mouth-wash’), limited to English-language clinical studies published from 2015 to 2025. Only English-language articles were considered. Papers that met the following inclusion criteria were double-blindly selected by the reviewers: (1) publications that involved human subjects and (2) clinical research, case studies, or randomized controlled trials (RCTs). Reviews and meta-analyses, research on animal models, and in vitro experiments fulfilled the exclusion criteria.

Table 1. P.I.C.O. criteria (population, intervention, comparison, outcome) flow diagram and database search indicators.

PICO Element	Description
Population (P)	Individuals with plaque-induced gingivitis; patients using mouthwashes and toothpastes for oral hygiene
Intervention (I)	Natural and herbal mouthwashes (Punicagranatum, Azadirachta indica, propolis, green tea, triphala, Guava); herbal toothpastes with plant-based antimicrobial agents
Comparison (C)	CHX (chlorhexidine) mouthwashes; fluoride-based toothpastes
Outcome (O)	Plaque reduction and gingival inflammation control; antimicrobial and anti-inflammatory effects; oral microbiota modulation; patient adherence, safety, and side effects

outlines the PICO (population, intervention, comparison, outcome) framework used to structure the clinical question of this systematic review. It clarifies the selection criteria applied during the database search, including the target population (patients with plaque-induced gingivitis), interventions (natural and herbal oral care products), comparators (conventional products like CHX and fluoride), and the outcomes assessed (e.g., plaque reduction, inflammation control, patient safety). This framework ensures transparency and reproducibility of the systematic review process.

2.2. Data Processing

Two authors (F.I. and D.D.V.) independently screened the titles and abstracts of the publications, and subsequently reviewed the full texts of those that met the inclusion criteria. Any articles that did not align with the topics investigated were excluded, with disagreements resolved by a third author (G.D.).

2.3. Data Extraction

Data extraction was carried out using a predefined data collection form by two independent reviewers (A.M.I. and A.D.I.).

The extracted variables included the following:

Type of study: randomized controlled trials (RCTs), crossover studies, and clinical trials;

Authors and year of publication;

Sample size: ranging from 20 to 135 participants across the studies;

Intervention type: natural products such as neem, green tea, aloe vera, propolis, miswak, cinnamon, Carica papaya, and polyherbal formulations;

Comparators: chlorhexidine (CHX) mouthwash, fluoride toothpaste, placebo formulations, and in some cases, no treatment controls;

Duration of the intervention: from 7 days to 6 months depending on the protocol.

The primary outcomes collected across the studies were as follows:

◦

Gingival index (GI);

◦

Plaque index (PI);

◦

Sulcular bleeding index (SBI);

◦

Papillary bleeding index (PB1);

◦

Interdental bleeding score (IBS).

Secondary outcomes included:

◦

Oral Hygiene Index-Simplified (OHI-s);

◦

Inflammatory biomarkers (e.g., IL-1ß, IL-6 in saliva, and GCF);

◦

Adverse effects (e.g., staining, taste alteration);

◦

Patient satisfaction and adherence.

Any discrepancies between reviewers were resolved by consensus or through third-party adjudication (G.M.).

2.4. Quality Assessment

Using ROBINS, a method designed to evaluate the risk of bias in the findings of non-randomized studies that compare the health effects of two or more interventions, three reviewers, V.C., R.V.G. and B.F.P.P., evaluated the quality of the included publications. Each of the seven assessed points was given a bias level.

The evaluated risk-of-bias domains were as follows:

• Bias due to confounding;
• Bias in selection of participants;
• Bias in classification of interventions;
• Bias due to deviations from intended interventions;
• Bias due to missing data;
• Bias in measurement of outcomes;
• Bias in selection of the reported result.

Assessment levels:

The overall risk of bias for each included study was determined by evaluating seven specific domains, such as participant selection, measurement of outcomes, and reporting.

Each study was categorized as having a low, moderate, or high risk of bias, based on the highest risk identified in any single domain.

Some studies were rated as having a low risk of bias across most or all domains. These studies demonstrated the following: the proper randomization of participants, the use of double-blind procedures to minimize subjective influence; and comprehensive reporting of outcome data with minimal attrition.

Some studies were rated as having a low risk of bias across most or all domains. These studies demonstrated the following: the proper randomization of participants; the use of double-blind procedures to minimize subjective influence; and comprehensive reporting of outcome data with minimal attrition.

These methodological strengths increase the internal validity and reliability of the findings.

Other studies showed a moderate risk of bias. Although they followed acceptable randomized controlled trial designs, they had methodological limitations, such as a lack of blinding for participants or outcome assessors (performance or detection bias).

These issues may have introduced bias, though the overall results remain informative:

A few non-randomized studies were rated as having a high risk of bias. The major concerns included the following:

The lack of randomization, which may lead to systematic differences between groups (selection bias); potential confounding, where differences in baseline characteristics could influence the outcomes.

These methodological flaws weaken the internal validity, limiting the reliability of the results.

2.5. Protocol and Registration

This systematic review adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The protocol was registered on PROS-PERO (The International Prospective Register of Systematic Reviews) under the reference number 1008296.

3. Results

Three databases were searched: PubMed (n = 54), Web of Science (n = 50), and Scopus (n = 1), for a total of 105 initial publications. After removing one duplicate, 104 articles were screened by title and abstract, resulting in the exclusion of 56 studies. Full-text assessment led to the exclusion of an additional 33 articles for not meeting the inclusion criteria.

In total, 15 studies were included in the qualitative analysis (Table 2). The selection process is summarized in the PRISMA flow diagram (Figure 1). Of the 15 included studies, 12 were randomized controlled trials (RCTs) and 3 were non-randomized controlled clinical trials. Sample sizes ranged from 20 to 135 participants, all diagnosed with plaque-induced gingivitis. The duration of the interventions ranged from 7 days to 6 months. The main clinical indicators evaluated were as follows: plaque index (PI), gingival index (GI), sulcular bleeding index (SBI), papillary bleeding index (PBI), and Oral Hygiene Index-Simplified (OHI-s). Some studies also assessed salivary inflammatory biomarkers (e.g., IL-1ß, IL-6), the occurrence of adverse effects (e.g., staining, taste alteration), and patient adherence to treatment.

Natural Products

Several studies evaluated the effectiveness of mouthwashes and toothpastes containing plant-based extracts.

Mouthwashes: Studies by Jalaluddin [43], Assiry [44], and Mahyari [45] reported a significant reduction in Pl and Gl with formulations containing Azadirachta indica, Illicium verum, or polyherbal extracts, showing efficacy comparable to CHX but with fewer side effects.

Toothpastes: Products based on Aloe vera, Carica papaya, turmeric, and miswak were tested by authors such as Hassan [46], Amano [47], and Azaripour [48], showing a significant reduction in gingival inflammation, comparable to toothpastes containing fluoride or triclosan.

Conventional Products

Chlorhexidine (CHX): Demonstrated high efficacy in reducing Pl and GI (Andhare, Zuttion) [49,50], but was frequently associated with dental staining and taste alteration.

Other chemical agents: Triratana [51] evaluated toothpastes containing triclosan and other antimicrobials, showing good efficacy but potential issues with tolerability and contraindications for long-term use.

Direct Comparison Between Natural and Conventional Products

Nine studies [43,44,45,47,48,49,50,51,52] directly compared natural and conventional oral care products. These studies evaluated outcomes such as plaque index, gingival index, bleeding indices, and patient-reported side effects. In general, natural products (e.g., neem, green tea, propolis, miswak) were found to be similarly effective in reducing clinical signs of gingivitis compared to CHX or fluoride-based products. Notably, natural products were associated with fewer adverse effects, such as staining and taste alteration, thereby enhancing long-term tolerability and patient compliance.

For example, Jalaluddin [43] compared neem mouthwash with 0.2% CHX and found similar reductions in PI and GI, with neem showing better tolerability. Jung [52] reported that a propolis and mangosteen extract complex significantly reduced inflammatory biomarkers and preserved the oral microbiota balance, unlike CHX. Andhare [49] demonstrated comparable results between green tea/aloe vera mouthwash and CHX, while Hassan [46] and Amano [47] confirmed the anti-inflammatory and antimicrobial efficacy of propolis-based toothpastes.

Table 2 presents a summary of the 15 studies included in the qualitative synthesis. It details the authors, type of study (RCT, crossover, clinical trial), objectives, materials and methods, and key outcomes or findings of each study. These studies evaluated a variety of natural and conventional toothpastes and mouthwashes, comparing their efficacy and safety in managing gingivitis. The table provides a clear comparative overview of the evidence base supporting the conclusions of the review.

Table 2. Featured studies in the qualitative analysis and their characteristics.

Author	Country	Type of Study	Sample Characteristics	Duration	Outcome	Material and Methods	Results
G. S. Zuttion et al. (2024) [50]	Brazil	RCT	Forty-four adults with gingivitis	Three weeks	Aimed to compare the antiplaque and antigingivitis efficacy of 0.12% CHX and 5% Malva sylvestris.	Forty-four participants were involved in two phases, each consisting of three stages with variations in the mouthwash solution used.	The results did not show statistically significant differences between the two groups regarding inflammation and plaque formation. However, CHX demonstrated a significantly greater average reduction in gingival inflammation compared to Malva (p = 0.02).
S. Mahyari et al. (2015) [45]	Iran	RCT	Sixty adults with gingivitis	Fourteen days	Investigated the effectiveness of a polyherbal mouthwash containing hydroalcoholic extracts compared to CHX-based mouthwashes and placebo in subjects with gingivitis.	Sixty patients were divided into three groups (polyherbal, CHX, placebo) and used the mouthwash twice a day for two weeks. Gingival and plaque indices were assessed at baseline, day 7, and day 14.	Significant improvements were observed in all effectiveness measures assessed in both the polyherbal mouthwash and CHX groups.
Md Jalaluddin et al. (2017) [43]	India	Crossover study	Forty-four adults with plaque-induced gingivitis	Two weeks	Aimed to evaluate the impact of neem-containing mouthwash on plaque and gingivitis.	It involved 40 participants, each randomly assigned to groups I and II. Group I was provided with 0.2% CHX gluconate, and group II received a 2% neem mouthwash.	There was a slight reduction in plaque levels in both the first and second phases.
V. Senkalvarayan et al. (2023) [53]	India	RCT	Forty-five healthy adults	Three weeks	Confirmed if mouthwashes with plant extract herbs possess anti-inflammatory, antimicrobial, and analgesic actions.	Forty-five subjects were selected and randomly divided into three groups, and the gingival index (GI), plaque index (PI), Oral Hygiene Index-Simplified (OHI-s) index, and Ainamo and Bay bleeding index were recorded.	Both CHX and herbal mouthwash have proven to be more effective than the placebo in maintaining gingival health.
M. G. Andhare et al. (2024) [49]	India	RCT	Sixty gingivitis patients	Twenty-one days	Evaluated the clinical efficacy of the 0.5% green tea (GT) mouthwash, 0.2% CHX mouthwash, and aloe vera (AV) mouthwash compared to the control group.	Sixty patients with generalized gingivitis were assigned to four study groups. The PI, GI, and sulcular bleeding index (SBI) were recorded at baseline, on day 14, and on day 21.	PI, GI, and SBI showed statistically significant differences within the CHX group (p < 0.01).
L. Z. Hassan et al. (2021) [46]	Iraq	Clinical study	Twenty adults	Seven days	The aim of this study was to evaluate the effects of a toothpaste containing propolis on plaque control and gingivitis both clinically and immunologically.	Twenty patients were selected to use propolis-containing toothpaste and a generic toothpaste for 7 days. A clinical periodontal evaluation and saliva samples were collected at baseline and after 7 days to estimate interleukin-1β and interleukin-6 levels.	The addition of propolis to toothpaste results in a greater reduction in plaque accumulation and inflammatory response.
A. Azaripouro et al. (2017) [48]	Germany	RCT	Sixty-six non-smoking adults	Three weeks	The effectiveness of a toothpaste containing miswak extract on gingival inflammation was evaluated.	Sixty-six non-smoker patients with bleeding ≥ 25% and pocket depth ≤ 3 mm were divided into three groups to use different toothpastes for 3 weeks. The primary outcome was bleeding after 21 days, with plaque measurement.	After 3 weeks of brushing, all three patient groups showed a significant reduction in SBI.
Terdphong Triratana et al. (2015) [51]	Thailand	RCT	One hundred and thirty-five adults with established gingivitis	Six months	To investigate the clinical efficacy of three toothpastes in controlling established gingivitis and plaque over 6 months.	One hundred and thirty-five subjects were assigned to one of the three treatments and were asked to use a different toothpaste. The subjects were instructed to brush their teeth twice a day for 1 min for 6 months.	Subjects assigned to the triclosan/copolymer/fluoride group showed statistically significant reductions in the GI and PI scores compared to those assigned to the herbal/baking soda group.
Jae-Suk Jung et al. (2024) [52]	South Korea	RCT	One hundred and four gingivitis/early periodontitis patients	Eight weeks	Examined the efficacy and safety of a propolis and mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and early periodontitis.	One hundred and four subjects received PMEC or a placebo for eight weeks. The main focus was on changes in inflammatory biomarkers in gingival crevicular fluid (GCF).	The results revealed that the PMEC group showed a significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p < 0.0001) at 8 weeks.
Ina Saliasi et al. (2018) [54]	Netherlands	RCT	Healthy subjects	Four weeks	The aim of this study was to determine the anti-inflammatory effects of a new Carica papaya leaf extract (CPLE) on interdental bleeding in healthy subjects.	Participants were divided into four groups and used different types of toothpaste and mouthwash for 4 weeks, maintaining their usual brushing habits. Interdental bleeding was measured at the beginning and after 3 weeks.	The CPLE toothpaste/mouthwash provides an effective and natural alternative to SLS-free toothpaste +/− mouthwash containing EO when used as a complement to mechanical oral hygiene to reduce interdental gingival inflammation.
Shigeru Amano et al. (2025) [47]	Japan	RCT	Forty-eight university students	Two weeks	The aim was to evaluate the effectiveness of toothpaste containing Brazilian green propolis (BGP) in improving the oral environment and identify its antibacterial compounds.	Forty-eight students were assigned to the BGP and placebo groups, receiving toothpaste with and without BGP, respectively. The plaque index PI score, gingival index GI score, and the proportion of periodontal pathogens on the tongue surface were analyzed at 0, 1, and 2 weeks.	We confirmed the effectiveness of propolis toothpaste in improving the oral microbiota, suggesting that BGP toothpaste is clinically useful for maintaining oral health and preventing periodontal disease.
Ali A. Assiry et al. (2021) [44]	Saudi Arabia	RCT	Fifty adults	Twenty-one days	The aim was to investigate the anti-inflammatory, astringent, and antimicrobial properties of an Illicium verum mouthwash.	Fifty subjects were divided into two groups, A (Illicium verum mouthwash) and B (placebo), and treated for 21 days. After 14 days, the mouthwashes were switched following a crossover design. GI, papillary bleeding index (PBI), and oral microbial count were recorded at each stage of the study.	The study revealed that the Illicium verum/star anise has potent antibacterial, anti-inflammatory, and astringent properties.
Thitiya Luetragoon et al. (2021) [55]	Thailand	RCT	Thirty-eight smokers	Not specified	Evaluated the effect of MO leaves and Cinnamomum Camphora (CC) extracts using MO tablets and a combination of MO + CC tablets on oral inflammation and gingivitis.	The included subjects were divided into two groups, one taking MO tablets and the other a combination of MO + CC tablets to assess the reduction in oral inflammation and gingivitis in smokers.	The MO tablets and MO + CC tablets reduced oral inflammation and gingivitis and showed potential for improving oral health in smokers.
S Arami et al. (2014) [56]	Iran	RCT	Twenty-eight gingivitis patients	Not specified	To evaluate the effectiveness of Pistacia atlantica var. mutica extract mouthwash on de novo dental plaque bacteria and subgingival microorganisms compared to CHX.	Twenty-eight patients were divided into two groups, one receiving P. atlantica and/or CHX and the other receiving the placebo.	To evaluate the effectiveness of Pistacia atlantica var. mutica extract mouthwash on de novo dental plaque bacteria and subgingival microorganisms compared to CHX.
Devanand Gupta et al. (2015) [57]	India	RCT	One hundred and five university students	Thirty days	To compare the effect of cinnamon extract, CHX mouthwash and placebo on dental plaque level and gingivitis.	One hundred and five students were randomly divided into three groups: the cinnamon group, the CHX gluconate mouthwash group, and the placebo group (distilled water). Data were collected at baseline, on day 15, and on day 30.	The results of the present study indicate that cinnamon may prove to be an effective agent owing to its ability to reduce plaque level and gingivitis.

Table 2. Featured studies in the qualitative analysis and their characteristics.

Author	Country	Type of Study	Sample Characteristics	Duration	Outcome	Material and Methods	Results
G. S. Zuttion et al. (2024) [50]	Brazil	RCT	Forty-four adults with gingivitis	Three weeks	Aimed to compare the antiplaque and antigingivitis efficacy of 0.12% CHX and 5% Malva sylvestris.	Forty-four participants were involved in two phases, each consisting of three stages with variations in the mouthwash solution used.	The results did not show statistically significant differences between the two groups regarding inflammation and plaque formation. However, CHX demonstrated a significantly greater average reduction in gingival inflammation compared to Malva (p = 0.02).
S. Mahyari et al. (2015) [45]	Iran	RCT	Sixty adults with gingivitis	Fourteen days	Investigated the effectiveness of a polyherbal mouthwash containing hydroalcoholic extracts compared to CHX-based mouthwashes and placebo in subjects with gingivitis.	Sixty patients were divided into three groups (polyherbal, CHX, placebo) and used the mouthwash twice a day for two weeks. Gingival and plaque indices were assessed at baseline, day 7, and day 14.	Significant improvements were observed in all effectiveness measures assessed in both the polyherbal mouthwash and CHX groups.
Md Jalaluddin et al. (2017) [43]	India	Crossover study	Forty-four adults with plaque-induced gingivitis	Two weeks	Aimed to evaluate the impact of neem-containing mouthwash on plaque and gingivitis.	It involved 40 participants, each randomly assigned to groups I and II. Group I was provided with 0.2% CHX gluconate, and group II received a 2% neem mouthwash.	There was a slight reduction in plaque levels in both the first and second phases.
V. Senkalvarayan et al. (2023) [53]	India	RCT	Forty-five healthy adults	Three weeks	Confirmed if mouthwashes with plant extract herbs possess anti-inflammatory, antimicrobial, and analgesic actions.	Forty-five subjects were selected and randomly divided into three groups, and the gingival index (GI), plaque index (PI), Oral Hygiene Index-Simplified (OHI-s) index, and Ainamo and Bay bleeding index were recorded.	Both CHX and herbal mouthwash have proven to be more effective than the placebo in maintaining gingival health.
M. G. Andhare et al. (2024) [49]	India	RCT	Sixty gingivitis patients	Twenty-one days	Evaluated the clinical efficacy of the 0.5% green tea (GT) mouthwash, 0.2% CHX mouthwash, and aloe vera (AV) mouthwash compared to the control group.	Sixty patients with generalized gingivitis were assigned to four study groups. The PI, GI, and sulcular bleeding index (SBI) were recorded at baseline, on day 14, and on day 21.	PI, GI, and SBI showed statistically significant differences within the CHX group (p < 0.01).
L. Z. Hassan et al. (2021) [46]	Iraq	Clinical study	Twenty adults	Seven days	The aim of this study was to evaluate the effects of a toothpaste containing propolis on plaque control and gingivitis both clinically and immunologically.	Twenty patients were selected to use propolis-containing toothpaste and a generic toothpaste for 7 days. A clinical periodontal evaluation and saliva samples were collected at baseline and after 7 days to estimate interleukin-1β and interleukin-6 levels.	The addition of propolis to toothpaste results in a greater reduction in plaque accumulation and inflammatory response.
A. Azaripouro et al. (2017) [48]	Germany	RCT	Sixty-six non-smoking adults	Three weeks	The effectiveness of a toothpaste containing miswak extract on gingival inflammation was evaluated.	Sixty-six non-smoker patients with bleeding ≥ 25% and pocket depth ≤ 3 mm were divided into three groups to use different toothpastes for 3 weeks. The primary outcome was bleeding after 21 days, with plaque measurement.	After 3 weeks of brushing, all three patient groups showed a significant reduction in SBI.
Terdphong Triratana et al. (2015) [51]	Thailand	RCT	One hundred and thirty-five adults with established gingivitis	Six months	To investigate the clinical efficacy of three toothpastes in controlling established gingivitis and plaque over 6 months.	One hundred and thirty-five subjects were assigned to one of the three treatments and were asked to use a different toothpaste. The subjects were instructed to brush their teeth twice a day for 1 min for 6 months.	Subjects assigned to the triclosan/copolymer/fluoride group showed statistically significant reductions in the GI and PI scores compared to those assigned to the herbal/baking soda group.
Jae-Suk Jung et al. (2024) [52]	South Korea	RCT	One hundred and four gingivitis/early periodontitis patients	Eight weeks	Examined the efficacy and safety of a propolis and mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and early periodontitis.	One hundred and four subjects received PMEC or a placebo for eight weeks. The main focus was on changes in inflammatory biomarkers in gingival crevicular fluid (GCF).	The results revealed that the PMEC group showed a significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p < 0.0001) at 8 weeks.
Ina Saliasi et al. (2018) [54]	Netherlands	RCT	Healthy subjects	Four weeks	The aim of this study was to determine the anti-inflammatory effects of a new Carica papaya leaf extract (CPLE) on interdental bleeding in healthy subjects.	Participants were divided into four groups and used different types of toothpaste and mouthwash for 4 weeks, maintaining their usual brushing habits. Interdental bleeding was measured at the beginning and after 3 weeks.	The CPLE toothpaste/mouthwash provides an effective and natural alternative to SLS-free toothpaste +/− mouthwash containing EO when used as a complement to mechanical oral hygiene to reduce interdental gingival inflammation.
Shigeru Amano et al. (2025) [47]	Japan	RCT	Forty-eight university students	Two weeks	The aim was to evaluate the effectiveness of toothpaste containing Brazilian green propolis (BGP) in improving the oral environment and identify its antibacterial compounds.	Forty-eight students were assigned to the BGP and placebo groups, receiving toothpaste with and without BGP, respectively. The plaque index PI score, gingival index GI score, and the proportion of periodontal pathogens on the tongue surface were analyzed at 0, 1, and 2 weeks.	We confirmed the effectiveness of propolis toothpaste in improving the oral microbiota, suggesting that BGP toothpaste is clinically useful for maintaining oral health and preventing periodontal disease.
Ali A. Assiry et al. (2021) [44]	Saudi Arabia	RCT	Fifty adults	Twenty-one days	The aim was to investigate the anti-inflammatory, astringent, and antimicrobial properties of an Illicium verum mouthwash.	Fifty subjects were divided into two groups, A (Illicium verum mouthwash) and B (placebo), and treated for 21 days. After 14 days, the mouthwashes were switched following a crossover design. GI, papillary bleeding index (PBI), and oral microbial count were recorded at each stage of the study.	The study revealed that the Illicium verum/star anise has potent antibacterial, anti-inflammatory, and astringent properties.
Thitiya Luetragoon et al. (2021) [55]	Thailand	RCT	Thirty-eight smokers	Not specified	Evaluated the effect of MO leaves and Cinnamomum Camphora (CC) extracts using MO tablets and a combination of MO + CC tablets on oral inflammation and gingivitis.	The included subjects were divided into two groups, one taking MO tablets and the other a combination of MO + CC tablets to assess the reduction in oral inflammation and gingivitis in smokers.	The MO tablets and MO + CC tablets reduced oral inflammation and gingivitis and showed potential for improving oral health in smokers.
S Arami et al. (2014) [56]	Iran	RCT	Twenty-eight gingivitis patients	Not specified	To evaluate the effectiveness of Pistacia atlantica var. mutica extract mouthwash on de novo dental plaque bacteria and subgingival microorganisms compared to CHX.	Twenty-eight patients were divided into two groups, one receiving P. atlantica and/or CHX and the other receiving the placebo.	To evaluate the effectiveness of Pistacia atlantica var. mutica extract mouthwash on de novo dental plaque bacteria and subgingival microorganisms compared to CHX.
Devanand Gupta et al. (2015) [57]	India	RCT	One hundred and five university students	Thirty days	To compare the effect of cinnamon extract, CHX mouthwash and placebo on dental plaque level and gingivitis.	One hundred and five students were randomly divided into three groups: the cinnamon group, the CHX gluconate mouthwash group, and the placebo group (distilled water). Data were collected at baseline, on day 15, and on day 30.	The results of the present study indicate that cinnamon may prove to be an effective agent owing to its ability to reduce plaque level and gingivitis.

4. Discussion

4.1. Comparison of Natural and Conventional Products: Clinical Efficacy

Plaque-induced gingivitis is a very common condition, and effective management requires products that can control both bacterial plaque and the inflammatory response.

Results of selected studies show that both conventional products (CHX, fluorides, triclosan) and natural products (e.g., neem, propolis, aloe vera, turmeric, cinnamon) are able to significantly reduce clinical indices of gingival inflammation (PI, GI, SBI, PBI). However, natural products appear to possess superior tolerability, with a lower incidence of side effects such as dental discoloration, taste alterations and mucosal irritation.

For instance, Jalaluddin found that both 0.2% CHX and 2% neem mouthwash led to a significant reduction in PI over two weeks (CHX: 36% reduction; Neem: 34% reduction; p < 0.05) [43]. Similarly, Zuttion’s study compared 0.12% CHX with 5% Malva sylvestris and reported that CHX led to a statistically greater reduction in gingival inflammation (mean GI reduction of 0.8 vs. 0.5, p = 0.02) [50]. However, the greater tolerability of Malva may favor its long-term use. Assiry confirmed the antibacterial and an-ti-inflammatory efficacy of Illicium verum, reporting a mean reduction in GI from 2.1 to 1.2 after three weeks, comparable to CH, emphasizing its preventive potential against periodontitis [44].

4.2. Grouping by Type of Intervention: Mouthwashes and Toothpastes

Natural mouthwashes, such as those studied by Mahyari (polyherbal formulation) and Andhare (green tea and aloe vera), showed comparable efficacy to CHX in reducing plaque and inflammation, but with greater acceptability by patients [45,49].

Senkalvarayan reported that herbal mouthwashes, although slightly less effective in reducing plaque than CHX, do not cause side effects and are therefore preferable for continued use [53].

With regard to toothpastes, Hassan showed that a formulation with propolis effectively reduced gingival inflammation and interleukin-1ß and interleukin-6 levels, compared to toothpastes [46]. Amano supported these data by demonstrating that a toothpaste with Brazilian green propolis improved the composition of the oral microbiota, favoring the selection of non-pathogenic bacteria [47].

Tolerability and Side-Effect Profile of Natural vs. Conventional Agents

While chlorhexidine (CHX) remains the gold standard for chemical plaque control, its side effects—especially dental staining, taste alteration, and mucosal irritation—limit long-term use. In contrast, most natural formulations reported in this review showed a significantly lower incidence of such effects [3,4]. For example, neem, aloe vera, and propolis-based products demonstrated similar efficacy with higher patient compliance and minimal adverse events. Comparative studies (e.g., Mahyari, Jalaluddin) highlight that although CHX may provide slightly faster results, natural agents are better suited for long-term and preventive care due to their safety profile [29,43,45,58,59].

4.3. Other Vehicles and Applications

More recent studies have also focused on alternative vehicles such as tablets or natural tablets. Luetragoon evaluated the efficacy of chewable tablets containing Moringa oleif-era and Cinnamomum camphora in smoking subjects, a population particularly resistant to conventional treatments. The results showed a significant reduction in gingival bleeding and inflammation (average GI reduction: 1.9 to 1.1; p < 0.01), with a good tolerability and acceptance profile. This study suggests that innovative formulations, other than traditional mouthwashes or toothpastes, may offer effective solutions for specific patient groups [55].

Arami, on the other hand, studied a toothpaste containing a combination of natural plant extracts in patients with chronic gingivitis. The product resulted in a significant reduction in PI and GI compared to the control group (PI from 2.3 to 1.4, GI from 2.1 to 1.3; p < 0.05), confirming the anti-inflammatory efficacy of the treatment [56]. Furthermore, participants reported high acceptability and no relevant side effects, reinforcing the potential of natural products as a viable alternative for the treatment of gingivitis in the long term [60].

Finally, Saliasi evaluated a toothpaste based on Carica papaya, reporting a reduction in interdental bleeding (a reduction of approximately 40%, similar to that observed with toothpastes containing essential oils), and Gupta reported an effective action of cinnamon on both plaque and inflammation, with good patient acceptance [54,57].

Selective Modulation of Oral Microbiota

Maintaining a balanced oral microbiome is critical to oral and systemic health. Natural formulations may selectively inhibit pathogenic species while preserving commensal flora, unlike CHX, which exhibits broad-spectrum antibacterial activity. Studies such as those by Jung and Amano demonstrated that propolis, green tea, and mangosteen extracts not only reduced pathogenic load but also supported eubiosis [47]. This selective modulation is especially valuable in avoiding dysbiosis-associated complications [61,62].

4.4. Microbiota Considerations and Patient Adherence

Jae-Suk Jung highlighted how a mouthwash containing propolis and mangosteen not only reduces inflammatory biomarkers in saliva, but also preserves the balance of the oral microbiota. This is relevant, as CHX tends to have an indiscriminate antibacterial action, which can compromise the beneficial flora [52].

The included studies show that natural products are more accepted by patients due to the better taste, lower incidence of adverse effects and the perceived ‘naturalness’ of the product. This may translate into better adherence to treatment, a critical element in the chronic management of gingivitis.

4.5. Mechanisms of Action of Natural Formulations

In addition to clinical outcomes, it is essential to understand how these natural agents work. Many herbal ingredients act through multiple biological mechanisms.

Green tea catechins, for example, can weaken bacterial membranes and inhibit plaque-forming enzymes such as glucosyltransferase. Propolis reduces inflammation by lowering levels of cytokines such as IL-1ß and TNF-a and supports tissue regeneration by stimulating fibroblast activity. Aloe vera, known for its healing properties, promotes collagen synthesis and protects tissues through its antioxidant effects. These combined actions contribute not only to symptom relief but also to a more balanced and resilient gingival environment.

Pharmacokinetics, Bioavailability, and Clinical Applicability of Herbal Agents

One key limitation of many natural formulations is the lack of well-characterized pharmacokinetic profiles. Factors such as absorption, salivary clearance, and systemic bioavailability of active compounds like EGCG (from green tea) or curcumin (from turmeric) are influenced by formulation techniques. Novel delivery systems (e.g., nanoemulsions, liposomes) may enhance bioavailability and retention time. Clinical acceptance is increasing, especially where patient preference favors “natural” products. However, consistent efficacy requires optimization of dosage forms and delivery strategies.

4.6. Methodological Quality and Reliability of Results

The assessment of the risk of bias using the ROBINS tool revealed that approximately one third of the studies had a low risk, another third a moderate risk (e.g., lack of blinding or limited follow-up), while some had a high risk, mainly due to the absence of randomization or too small samples (

Table 3. Bias assessment using the Robins tool.

Authors (Year)	D1	D2	D3	D4	D5	D6	D7	Overall
G. S. Zuittion et al. (2024) [50]
S. Mahyari et al. (2015) [45]
M.D. Jalaluddin et al. (2017) [43]
V. Senkalvarayan et al. (2023) [53]
M.G. Andhare et al. (2024) [49]
L. Z. Hassan et al. (2021) [46]
U. Azaripouro et al. (2017) [48]
T. Triratana et al. (2015) [51]
Jae-Suk Jung et al. (2024) [52]
I. Saliasi et al. (2018) [54]
Shigeru Amano et al. (2025) [47]
Ali A. Assiry et al. (2021) [45]
T. Luetragon et al. (2021) [55]
S. Arami et al. (2014) [56]
D. Gupta et al. (2015) [57]

Domains: D1: Bias due to confounding. D2: Bias arising from measurement of the exposure. D3: Bias in the selection of participants for the study (or for the analysis). D4: Bias due to post-exposure interventions. D5: Bias due to missing data. D6: Bias arising from measurement of the outcome. D7: Bias in selection of the reported result. Very high. High. Some concerns. Low. No information.

).

Low-risk studies, such as those of Mahyari, Andhare and Jung, offer the strongest evidence, whereas data from high-risk studies must be interpreted with caution [45,49,52].

Furthermore, the heterogeneity in protocols (duration, concentration, formulations) limits the possibility of quantitative meta-analyses and direct comparisons.

4.7. Recommendation for Natural Formulation Standardization

To ensure natural oral care products achieve consistent clinical outcomes, their development should be guided by standardized procedures. These include specifying the effective dosage ranges for active compounds, using reproducible extraction techniques, and enforcing robust quality control during manufacturing. Future clinical trials should adopt unified criteria—such as common plaque and GI metrics—to allow for reliable comparisons across studies. Regulatory bodies should also define clear evidence-based guidelines for evaluating the safety and effectiveness of herbal formulations before market approval.

Quality Control and Batch-to-Batch Standardization

One of the main challenges in the clinical application of herbal oral care products is ensuring consistency and reproducibility between production batches. Herbal extracts are highly susceptible to variation due to environmental, agricultural, and processing factors. This variability affects the concentration, potency, and efficacy of the active phytochemicals in the final product.

To address this issue, manufacturers must adopt standardized protocols for sourcing, processing, and testing botanical raw materials. The following strategies are recommended:

Phytochemical fingerprinting: Techniques such as high-performance liquid chromatography (HPLC), gas chromatography–mass spectrometry (GC-MS), or liquid chromatography–mass spectrometry (LC-MS) should be used to profile the specific bioactive compounds (e.g., EGCG in green tea, eugenol in clove, curcumin in turmeric) to ensure consistency across batches.

Quantification of active markers: Manufacturers should define and monitor target concentration ranges for known active constituents. For example, propolis-based products might be standardized to a fixed percentage of total flavonoids or polyphenols.

Good Manufacturing Practices (GMP): Production should follow GMP guidelines specific to herbal pharmaceuticals, including controlled environmental conditions, traceability of raw materials, and validated extraction methods.

Stability testing: Each batch should be evaluated for shelf stability under various storage conditions to confirm that active constituents remain effective over the product’s lifecycle.

Microbiological and contamination control: As natural extracts may carry microbial or pesticide residues, rigorous quality assurance protocols are necessary to meet safety thresholds.

Regulatory alignment: Efforts should align with guidelines from authoritative bodies such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA) concerning botanical drugs or supplements.

Establishing these controls is essential not only for maintaining therapeutic consistency but also for building clinician and consumer trust in natural oral care products. Without proper standardization, variability in formulation may lead to inconsistent clinical outcomes, limiting widespread adoption despite favorable initial evidence.

4.8. Limitations of Natural Formulation

While natural oral care products offer encouraging benefits—such as fewer side effects and better tolerability—they still face some important limitations that make them less suitable as a first-line choice (150–153). One major issue is inconsistency: the concentration of active compounds can vary depending on how and where the plants were grown or processed. This makes it difficult to guarantee the same effect across different batches or brands. Moreover, strong scientific evidence from large and long-term clinical trials is still lacking for many of these formulations. It should also be noted that, due to the predefined selection and exclusion criteria applied in this review (e.g., the time criterion), the number of retrieved studies for certain natural components—such as propolis or polyphenols—may have been reduced, potentially affecting their representativeness compared with other, more recently investigated substances. Acknowledging these limitations is an integral part of the scientific process and ultimately strengthens the robustness and applicability of the present findings, contributing to further technological and clinical development.

4.9. Future Perspectives and Necessary Research

The potential of natural products in the management of gingivitis is evident, but further research remains necessary to carry out the following:

◦

Standardize plant-based formulations;

◦

Establish optimal dosages and application times;

◦

Assess long-term efficacy;

◦

Directly compare natural and conventional formulations in high-quality multi-center studies;

◦

Analyze the impact on cost and environmental sustainability.

Furthermore, the role of natural products in selectively modulating the microbiota could be an important factor to research further.

5. Conclusions

Current evidence suggests that natural oral care products may serve as viable alternatives to conventional toothpastes and mouthwashes for managing gingivitis. While CHX and fluoride-based formulations remain standard treatments for plaque control and inflammation management, plant-derived extracts have demonstrated comparable efficacy, with fewer side effects and improved patient compliance.

To establish broader recommendations, further standardization of natural product formulations and long-term clinical studies are required to confirm their effectiveness in preventing gingivitis and stabilizing the oral microbiota. Future research should focus on optimizing plant extract combinations, evaluating their long-term impact, and integrating them into evidence-based oral health guidelines.