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Introduction: Agni, the concept of digestive and metabolic fire in Ayurveda, is regarded as the foundation of health and disease. It governs digestion, absorption, assimilation, and transformation of nutrients. Contemporary biomedicine explains these processes through metabolism and enzymology, highlighting parallels between ancient theories and modern physiology. Methods: A comprehensive review was conducted by analyzing classical Ayurvedic texts (Charaka Samhita, Sushruta Samhita, Ashtanga Hridaya), PubMed, Scopus, and Web of Science databases. Inclusion criteria comprised original research, reviews, and experimental studies (2000–2024) correlating Agni with digestion, enzymes, metabolism, and systemic health. Exclusion criteria included non-peer-reviewed sources and studies lacking methodological rigor. Results: Ayurveda classifies Agni into 13 types—Jatharagni (digestive), Bhutagni (elemental), and Dhatvagni (tissue-specific)—emphasizing its systemic role. Disorders of Agni (Mandagni, Tikshnagni, Vishamagni, Samagni) correlate with metabolic dysfunctions, enzyme imbalance, oxidative stress, and gastrointestinal diseases. Modern research links poor digestive efficiency to conditions like metabolic syndrome, obesity, diabetes, and inflammatory bowel disorders. Experimental studies show correlations between impaired enzymatic activity and Ayurvedic descriptions of deranged Agni. Additionally, interventions such as herbal formulations, dietary practices, and Panchakarma therapies modulate enzymatic activity and metabolic balance. Discussion: Parallels between Agni and modern metabolism emphasize holistic health through digestive and enzymatic regulation. Despite promising overlaps, translational gaps exist due to differences in terminologies, methodologies, and biomarkers. Conclusion: Understanding Agni in light of modern enzymology and metabolism provides a bridge between Ayurveda and contemporary biomedical sciences. Further integrative research can establish biomarkers of Agni and strengthen Ayurveda’s relevance in metabolic health.

KEYWORDS: Agni, Ayurveda, digestion, enzymology, metabolism