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ObjectivesExosomes derived from stem cells are a potential cell‐free tool for tissue regeneration with therapeutic potential. However, its application in cementum repair is unclear. This study aimed to investigate the effect of human periodontal ligament stem cell‐derived exosomes on the biological activity of cementoblasts, the main effector cells in cementum synthesis.Materials and MethodsOCCM‐30 cementoblasts were cultured with various human periodontal ligament stem cell‐derived exosome concentrations. OCCM‐30 cells proliferation, migration, and cementogenic mineralization were examined, along with the gene and protein expression of factors associated with cementoblastic mineralization.ResultsExosomal promoted the migration, proliferation, and mineralization of OCCM‐30 cells. The exosome‐treated group significantly increased the expression of cementogenic‐related genes and proteins. Furthermore, the expression of p‐PI3K and p‐AKT was enhanced by exosome administration. Treatment with a PI3K/AKT inhibitor markedly attenuated the gene and protein expression of cementoblastic factors, and this effect was partially reversed by exosome administration.ConclusionsHuman periodontal ligament stem cell‐derived exosomes can promote the activity of cementoblasts via the PI3K/AKT signaling pathway, providing a scientific basis for promoting the repair process in orthodontically induced inflammatory root resorption.