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Introduction: Panchakarma, a cornerstone of Ayurveda, is described as a comprehensive detoxification and rejuvenation therapy aimed at eliminating accumulated Ama (toxic byproducts) and restoring physiological equilibrium. With the rise of lifestyle disorders and toxin-related diseases, there is renewed interest in Panchakarma as a holistic detox approach. Modern science has begun to investigate its mechanisms and outcomes, offering biochemical and clinical evidence for its effects. Methods: A systematic review of literature was undertaken using PubMed, Scopus, Web of Science, AYUSH Research Portal, and Google Scholar. Ayurvedic classical texts (Charaka Samhita, Sushruta Samhita, Ashtanga Hridaya) were also examined. Studies published between 2000–2024 were included if they evaluated Panchakarma in relation to detoxification, metabolic correction, or systemic health improvement. Both clinical and experimental studies were reviewed. Results: Panchakarma therapies such as Virechana, Vamana, Basti, Nasya, and Raktamokshana demonstrated significant outcomes in detoxification processes. Clinical trials reported improvements in lipid profile, inflammatory markers, oxidative stress parameters, and heavy metal clearance. Modern investigations highlight its influence on gut microbiota modulation, liver enzyme normalization, and cortisol regulation. Experimental studies support mechanisms including reduced reactive oxygen species, cytokine modulation, and enhanced antioxidant activity. Discussion: Panchakarma overlaps conceptually with modern detoxification strategies such as chelation, antioxidant therapy, and microbiome modulation. However, heterogeneity in protocols, small sample sizes, and lack of standardized biomarkers limit its universal acceptance. Future studies with omics-based approaches and multicenter randomized controlled trials (RCTs) are necessary. Conclusion: Panchakarma represents a scientifically relevant and integrative detoxification strategy, bridging Ayurveda with modern medicine. With further validation, it has the potential to contribute significantly to global health practices.

KEYWORDS: Ayurveda, Detoxification, Panchakarma, Oxidative stress, Toxicology