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This review provides a comprehensive overview of the discovery and evolution of Tregs, detailing their immunoregulatory mechanisms that underpin their therapeutic potential. We systematically evaluate current clinical applications of Treg therapy in diverse non-tumor pathologies, highlighting both the efficacy and safety outcomes reported in ongoing clinical trials. Additionally, the review addresses the challenges faced in translating Treg therapies from bench to bedside, such as cell stability, expansion methodologies, and functional heterogeneity. Finally, we explore future directions in Treg research, including innovative therapeutic approaches, advances in gene engineering technologies, and improvements in cell expansion techniques, all aimed at enhancing the clinical translation and therapeutic efficacy of Treg-based interventions. 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