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Introduction: Panchakarma, the fivefold detoxification therapy in Ayurveda, is considered one of the most effective modalities for chronic and lifestyle-related diseases. In recent decades, there has been a growing interest in validating its efficacy through clinical trials. However, the heterogeneity of methodologies and lack of standardized protocols raise questions regarding scientific rigor. Methods: A systematic review was conducted using PubMed, Scopus, Web of Science, AYUSH Research Portal, and Google Scholar. Clinical trials published between 2000 and 2024 were included. Classical Ayurvedic texts (Charaka Samhita, Sushruta Samhita, Ashtanga Hridaya) were also examined to compare traditional indications with modern trial designs. Inclusion criteria comprised randomized controlled trials (RCTs), open-label studies, and pilot trials on Panchakarma interventions. Case reports and studies lacking methodological clarity were excluded. Results: Analysis revealed that clinical trials on Panchakarma have primarily focused on neurological disorders (stroke, migraine), metabolic disorders (obesity, diabetes, dyslipidemia), musculoskeletal conditions (osteoarthritis, low back pain), and gynecological problems (PCOS, infertility). Panchakarma interventions such as Virechana, Basti, Vamana, Nasya, and Raktamokshana were evaluated both individually and in combination with herbal therapy. Most trials reported symptomatic relief, improved quality of life, biochemical improvement, and reduction in disease progression. However, many lacked adequate sample size, blinding, and follow-up. Discussion: While clinical trials demonstrate promising outcomes, methodological flaws limit generalizability. Bridging Ayurvedic principles with modern trial methodology is essential for evidence-based validation of Panchakarma. Conclusion: Clinical trials on Panchakarma highlight its therapeutic potential across diverse diseases, but future research must adopt rigorous multicenter RCT designs, standardized outcome measures, and mechanistic studies for global acceptance.

KEYWORDS: Ayurveda, Clinical trials, Detoxification, Panchakarma, Randomized controlled trials