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Introduction: Knee osteoarthritis (OA) is a degenerative joint disease that affects millions globally, causing chronic pain and limited mobility. Pharmacological treatments for OA-related knee pain come with risks, making alternative or complementary therapies attractive. This post-market trial evaluates the efficacy of Puressentiel^® Muscles and Joints gel, an aromatherapy gel with 14 essential oils, in managing OA-related knee pain. Method: In this 12-week open-label trial (NCT04736563), participants aged 45–90 with OA-related knee pain applied Puressentiel^® Muscles and Joints gel twice daily for 4 weeks, following a 4-week run-in period without treatment. Pain, joint stiffness, and function were assessed using the Western Ontario McMaster Universities Arthritis Index (WOMAC) and Visual Analog Scale (VAS) at baseline, 4 weeks, 8 weeks, and 12 weeks, and oral analgesic intake was recorded daily. Results: Significant improvements in WOMAC and VAS scores were observed during treatment (p = 0.0262; p < 0.0001, respectively) and sustained 4 weeks post-treatment (p = 0.0190; p < 0.0001, respectively). Paracetamol intake significantly decreased from baseline to the end of treatment (p = 0.0230), though anti-inflammatory intake did not change significantly. No adverse events were reported. Conclusion: Puressentiel^® Muscles and Joints gel was well-tolerated, improved WOMAC and VAS scores, and reduced paracetamol use, presenting a viable natural option for pain management in knee OA. Full article