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Introduction: The immune system plays a central role in health and disease, influencing susceptibility to infections, chronic inflammatory conditions, autoimmune disorders, and metabolic syndromes. Ayurveda, the ancient Indian system of medicine, emphasizes Ojas and Vyadhikshamatva as concepts comparable to immunity. Panchakarma, a fivefold detoxification and rejuvenation therapy, is described as a cornerstone intervention for maintaining systemic balance and resilience. Modern research increasingly explores its immunomodulatory potential. Methods: A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, AYUSH Research Portal, and Google Scholar, alongside Ayurvedic classical texts (Charaka Samhita, Sushruta Samhita, Ashtanga Hridaya). Studies published between 1990 and 2024, including clinical trials, experimental studies, systematic reviews, and conceptual research on Panchakarma and immune function, were included. Exclusion criteria were poor-quality studies, unrelated interventions, and duplicate reports. Results: Panchakarma procedures such as Virechana, Basti, Vamana, and Nasya demonstrate immunoregulatory effects through detoxification, reduction of inflammatory cytokines, modulation of gut microbiota, enhancement of antioxidant status, and improved stress resilience. Clinical trials report benefits in conditions like rheumatoid arthritis, psoriasis, asthma, and metabolic syndrome. Experimental studies reveal influences on T-cell activity, immunoglobulin levels, and cytokine profiles. Panchakarma in combination with Rasayana therapy further strengthens immune homeostasis. Discussion: Panchakarma aligns with modern concepts of immunomodulation by promoting detoxification, reducing oxidative stress, regulating the gut–immune axis, and restoring neuroendocrine balance. Despite promising evidence, limitations include small sample sizes, heterogeneity in protocols, and lack of standardized outcome measures. Conclusion: Panchakarma offers significant promise as an integrative immunomodulatory strategy. Robust clinical trials and mechanistic studies are required to establish its role in preventive and therapeutic immunology.

KEYWORDS: Ayurveda, Detoxification, Immunomodulation, Panchakarma, Vyadhikshamatva