Abstract: Regulatory T cells (Treg cells) are the most important population of immune cells for maintaining peripheral immune tolerance in the body. Targeting Treg cells to rebuild peripheral immune tolerance has broad application prospects in the treatment of various inflammatory diseases such as autoimmune diseases (AIDs), allergic diseases, graft-versus-host disease (GVHD), and organ transplant rejection. However, Treg cell therapy still faces many challenges in clinical translation. In this review, we first described the discovery of Treg cells and summarized the main mechanisms by which Treg cells inhibit immune responses. Then, the research progress of polyclonal Treg cell therapy, autoantigen-specific Treg cell therapy, low-dose IL-2 therapy and the implementation of clinical trials were comprehensively summarized; Finally, we emphasized that maintaining the stability of Treg cells, preparing autoantigen-specific Treg cells such as CAR-Treg and TCR-Treg cells, reshaping the inflammatory microenvironment of diseases, and overcoming the "side effects" of Treg cell therapy are the bottleneck problems in the clinical translation of Treg cell therapy and key directions for future research.