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Panchakarma is a sequence of purificatory and rejuvenative procedures whose rationale is expressed in classical concepts such as Agni, Ama, Srotas and Dosha. Translating these concepts into measurable biology is a central challenge for integrative research. This article reviews hypotheses and early evidence linking Panchakarma to three domains of contemporary biology: the gut microbiome, systemic inflammation and epigenetic or transcriptomic regulation. Metabolomic data from a Panchakarma-based programme demonstrate systemic biochemical shifts, and mechanistic literature on diet, microbiota, inflammation and mind–body practice provides plausible frameworks. Direct studies of procedure-specific effects, such as Vamana, Virechana and Basti on microbiota or epigenetic markers, remain scarce. A research agenda built on systems biology, Ayurgenomics and well-controlled designs is proposed.