Abstract <p>Periodontitis is a chronic infectious disease characterized by the destruction of periodontal supporting tissues. Traditional treatment methods, including scaling and root planing, have limited effectiveness in restoring damaged periodontal tissues, necessitating the exploration of new periodontitis treatment strategies. Recently, the transplantation of mesenchymal stem cells (MSCs) has made some progress in periodontitis treatment. However, scholars have found that exogenous MSCs undergo substantial apoptosis shortly after transplantation, complicating the understanding of MSCs’ specific mechanisms of action in periodontitis treatment. Notably, recent studies have reported that cells post-apoptosis can exert therapeutic effects through apoptotic vesicles (ApoVs). Several studies have confirmed that ApoVs derived from MSCs (MSC-ApoVs) have potential therapeutic effects in various disease models through immunomodulation, inflammation suppression, tissue regeneration, and drug delivery. Considering that immunomodulation, inflammatory response, and tissue regeneration are core objectives of periodontitis treatment, MSC-ApoVs show broad application prospects. This review discusses the research progress and application potential of MSC-ApoVs in the field of periodontitis treatment and compares their significant advantages over traditional stem cell transplantation techniques. This review also deepens our understanding of the mechanisms of action of MSC-ApoVs and guides us in their future clinical applications in periodontitis treatment.</p> Graphical abstract <p>Illustration depicts MSC-apovs tailoring and effects MSC-apovs on functions of various cells present in periodontal tissues which indicate tremendous application potential of MSC-apovs in periodontitis treatment. Created by figdraw</p> <p></p>