This review discusses the application of mesenchymal stem/stromal cells (MSCs) in periodontal regeneration, highlighting both preclinical and clinical studies. MSCs, derived from various sources such as non-odontogenic and odontogenic tissues, and induced pluripotent stem cells (iPSCs), have shown promise in improving periodontal tissue regeneration. The transplantation procedures, including the use of biomaterials and scaffold-free methods, are discussed, along with the therapeutic mechanisms and concerns related to the effectiveness and safety of MSCs. Despite the potential benefits, challenges such as surgical indications, complications, and ethical issues remain. The review also addresses the heterogeneity and immune compatibility of MSCs, emphasizing the need for further research to standardize and optimize their clinical application. Overall, while MSCs show promise, more research is needed to fully realize their potential in periodontal regeneration.This review discusses the application of mesenchymal stem/stromal cells (MSCs) in periodontal regeneration, highlighting both preclinical and clinical studies. MSCs, derived from various sources such as non-odontogenic and odontogenic tissues, and induced pluripotent stem cells (iPSCs), have shown promise in improving periodontal tissue regeneration. The transplantation procedures, including the use of biomaterials and scaffold-free methods, are discussed, along with the therapeutic mechanisms and concerns related to the effectiveness and safety of MSCs. Despite the potential benefits, challenges such as surgical indications, complications, and ethical issues remain. The review also addresses the heterogeneity and immune compatibility of MSCs, emphasizing the need for further research to standardize and optimize their clinical application. Overall, while MSCs show promise, more research is needed to fully realize their potential in periodontal regeneration.