Background: In the evolving paradigm of green pharmacology, Terminalia arjuna is emerging as a potent, bio-inspired solution for tackling kidney stone disease (urolithiasis). Revered in Ayurveda for its cardioprotective and nephroprotective properties, T. arjuna is now positioned as a multidisciplinary powerhouse in the realm of smart, sustainable therapeutics. Its complex phytochemical landscape, enriched with arjunic acid, flavonoids, and saponins, drives a holistic approach to treating urolithiasis by addressing not only the stones but also the underlying metabolic and oxidative imbalances. Methods: This review integrates quantum molecular modeling, artificial intelligence (AI)-powered predictive analytics, and nanopharmacology to explore T. arjuna’s multifaceted action against kidney stones. Through advanced computational simulations, the interactions of T. arjuna’s active compounds with stone-forming molecules are mapped, while cutting-edge nanocarrier systems and bio-nanotechnology are explored for enhancing targeted renal delivery. The review also delves into the biomolecular and genomic pathways modulated by T. arjuna in preventing stone formation and enhancing renal tissue regeneration. Results: T. arjuna offers an innovative, multi-pronged attack against urolithiasis, leveraging its antioxidant, anti-inflammatory, and crystallization-modifying properties. AI-driven modeling identifies its molecular binding sites in the renal system, while smart nanostructures increase bioavailability and tissue specificity. Evidence from in-vitro and in-vivo studies underscores its ability to prevent stone formation, dissolve existing stones, and promote renal regeneration. Conclusion: Terminalia arjuna transcends its historical roots, emerging as a bio-digital hybrid in renal therapeutics. By merging AI, nanotechnology, and plant-based precision medicine, it promises a personalized, eco-sustainable future in kidney stone management.