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Introduction: Rasa Shastra, the branch of Ayurveda dealing with minerals, metals, and herbo-mineral preparations, has played a transformative role in the evolution of Indian medicine. Its roots trace back to the early alchemical practices of Nagarjuna, a pioneer of Rasayana Tantra, and continue to influence contemporary Ayurvedic pharmaceutics. Despite its long tradition, Rasa Shastra is often debated for its safety, scientific validation, and integration with modern pharmacology. Methods: A comprehensive literature review was conducted using classical Ayurvedic texts (Charaka Samhita, Sushruta Samhita, Rasaratnakara, Rasarnava, and Rasashastra treatises), published peer-reviewed journals (PubMed, Scopus, Web of Science), and modern pharmacological studies. Inclusion criteria involved historical, pharmacological, and clinical studies on Rasa Shastra formulations, while irrelevant or non-authentic sources were excluded. Results: The review highlights Nagarjuna’s pioneering role in systematizing the use of mercury and other metals, followed by the medieval expansion of Rasashastra texts between the 8th–13th centuries CE. It also outlines the refinement of Shodhana (purification) and Marana (calcination) techniques, ensuring safety and bioavailability of formulations. In the colonial and modern era, Rasa Shastra was criticized for toxicity concerns but later regained relevance due to advanced analytical tools such as XRD, SEM, ICP-MS, and pharmacological validation of formulations like Rasasindura and Swarna Bhasma. Discussion: While Rasa Shastra demonstrates profound therapeutic utility, challenges remain in standardization, safety validation, and clinical integration. Modern pharmaceutics and nanotechnology offer avenues for bridging tradition with evidence-based science. Conclusion: From its roots in alchemy to its contemporary position in integrative medicine, Rasa Shastra has demonstrated resilience and adaptability. Its future lies in harmonizing traditional wisdom with modern scientific rigor for safe, effective, and globally acceptable therapeutics.

KEYWORDS: Alchemy, Ayurveda, Bhasma, Nagarjuna, Rasa Shastra