Periodontitis (PD), also known as gum disease, is a condition causing inflammatory bone resorption and tooth loss. Regulatory T cells (Tregs) and regulatory B cells (Bregs) are vital in controlling the immune response and hence play a role in infections and peripheral tolerance adjustment. These cells have immunosuppressive and tissue-repairing capabilities that are important for periodontal health; however, in inflammatory circumstances, Tregs may become unstable and dysfunctional, accelerating tissue deterioration. In recent years, Regulatory cell-mediated immunotherapy has been shown to be effective in many inflammatory diseases. Considering the roles of Tregs and Bregs in shaping immune responses, this study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the role of regulatory T and B cells, as well as their therapeutic applications in PD.