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Introduction: Stress-related disorders are increasingly prevalent in modern society, contributing to neuroendocrine dysregulation, immune dysfunction, and chronic diseases. Ayurveda describes several herbs with Rasayana properties, many of which act as adaptogens—agents that enhance the body’s nonspecific resistance to stress while maintaining homeostasis. Modern pharmacology has recognized adaptogens such as Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi), and Ocimum sanctum (Tulsi) as key candidates in stress regulation. Methods: A systematic review was conducted using Ayurvedic classics (Charaka Samhita, Sushruta Samhita, Ashtanga Hridaya, Bhavaprakasha) and modern databases (PubMed, Scopus, Web of Science, AYUSH Research Portal). The search terms included “adaptogens,” “Rasayana,” “stress pharmacology,” and “Ayurveda.” Inclusion criteria comprised pharmacological, toxicological, and clinical studies published in English between 1990–2025. Results: Ayurvedic Rasayana herbs demonstrate adaptogenic actions by modulating the hypothalamic-pituitary-adrenal (HPA) axis, balancing cortisol levels, enhancing mitochondrial resilience, and improving immune and cognitive function. For instance, Ashwagandha reduces stress-induced hypercortisolemia, while Guduchi enhances antioxidant defense and immune surveillance. Tulsi regulates neurotransmitter balance and reduces anxiety. Clinical studies support their efficacy in conditions like anxiety, depression, metabolic syndrome, and chronic fatigue. However, variability in study design, dosage, and standardization limits cross-comparison. Discussion: Ayurveda’s holistic framework of Rasayana corresponds closely with modern adaptogen research, both emphasizing homeostasis and resilience. Future directions include molecular profiling, multi-omics approaches, and standardized clinical trials to validate integrative stress-management protocols. Conclusion: Adaptogens in Ayurveda offer a robust and safe approach for stress resilience. Bridging traditional concepts with modern pharmacological insights may enhance therapeutic strategies for stress-related disorders.

KEYWORDS: Adaptogens, Ayurveda, Rasayana, stress pharmacology, Withania somnifera