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Introduction: Rasashastra, a specialized branch of Ayurveda, emphasizes the therapeutic use of metals, minerals, and herbo-mineral formulations. Despite its long-standing role in clinical practice, skepticism persists regarding safety and efficacy due to inadequate standardization and limited integration with evidence-based biomedical frameworks. Methods: A systematic literature review was conducted by searching PubMed, Scopus, AYUSH Research Portal, Google Scholar, and Web of Science databases (2000–2025). Classical Ayurvedic texts including Rasatarangini, Rasamritam, and Charaka Samhita were also reviewed. Keywords included “Rasashastra,” “herbo-mineral formulations,” “Ayurveda pharmacology,” “toxicology,” and “evidence-based medicine.” Studies were included if they presented pharmacological, toxicological, preclinical, or clinical data on Rasashastra formulations. Exclusion criteria included non-peer-reviewed sources and anecdotal reports. Results: Evidence indicates that Rasashastra formulations, when subjected to classical Shodhana (purification) and Marana (incineration) processes, exhibit significant reduction in toxicity and enhanced bioavailability. Preclinical studies demonstrate promising antioxidant, anti-inflammatory, antimicrobial, and anticancer activities of formulations such as Abhraka Bhasma, Swarna Bhasma, and Rasasindura. Clinical evidence supports efficacy in chronic diseases including arthritis, asthma, and metabolic disorders. Advances in nanotechnology validate that many bhasmas contain nanoparticles with unique therapeutic properties. Discussion: Rasashastra aligns with contemporary concepts of nanomedicine and personalized therapeutics. However, challenges include variability in manufacturing practices, lack of large-scale clinical trials, and insufficient global regulatory recognition. Bridging these gaps requires harmonization of traditional methods with modern analytical tools, toxicological profiling, and pharmacovigilance systems. Conclusion: An evidence-based approach to Rasashastra can provide a strong foundation for its global acceptance in integrative medicine. Rigorous clinical trials, modern pharmaceutics, and translational research will be pivotal in bridging traditional wisdom with contemporary science.

KEYWORDS: Ayurveda, Evidence-based medicine, Nanomedicine, Rasashastra, Safety