Abstract: Peripheral immune tolerance serves as a core mechanism for maintaining immune homeostasis within the body. Regulatory T cells (Tregs) are the key cells responsible for performing this function. Through cell-contact-dependent mechanisms, secretion of inhibitory cytokines, and metabolic interference, Tregs actively suppress the activation of effector immune cells. In the local oral environment, the dynamic balance of the Treg/T helper cell 17 (Th17) axis is of crucial importance for maintaining oral health and represents a common immunopathological basis for various oral diseases. In periodontitis, the excessive activation of Th17 cells and the suppression of Treg function trigger chronic destructive inflammation and alveolar bone resorption. In mucosal diseases such as oral lichen planus and recurrent aphthous ulcers, the disorder of the Treg/Th17 axis results in pathological autoimmune attacks. In oral squamous cell carcinoma, the tumor microenvironment recruits Tregs to establish abnormal immune tolerance, which mediates immune escape and promotes tumor progression. Based on these findings, therapeutic strategies targeting the precise regulation of Treg function or the reshaping of the Treg/Th17 balance are emerging, including cytokine modulators, small molecule drugs, and engineered Treg cell therapies. However, current research continues to encounter bottlenecks, including the unclear mechanism of Tregs heterogeneity and the challenge of achieving both high targeting efficiency and safety in clinical translation. In the future, it is essential to integrate multi-omics technologies to comprehensively analyze the immune regulatory network within the oral microenvironment and develop precise delivery systems to facilitate clinical translation. This article conducts a systematic review of the mechanism of peripheral immune tolerance and the role of Tregs in oral diseases, thoroughly analyzes the characteristics of immune dysregulation in different diseases, and deliberates on the therapeutic strategies based on immune tolerance regulation and their clinical application prospects, aiming to provide a theoretical foundation for precise immune therapy of oral diseases.