Bone regeneration is a crucial part in the treatment of periodontal tissue regeneration, in which new attempts come out along with the development of nanomaterials. Herein, the effect of cerium oxide nanoparticles (CeO NPs) on the cell behavior and function of human periodontal ligament stem cells (hPDLSCs) was investigated. Results of CCK-8 and cell cycle tests demonstrated that CeO NPs not only had good biocompatibility, but also promoted cell proliferation. Furthermore, the levels of alkaline phosphatase activity, mineralized nodule formation and expressions of osteogenic genes and proteins demonstrated CeO NPs could promote osteogenesis differentiation of hPDLSCs. Then we chose electrospinning to fabricate fibrous membranes containing CeO NPs. We showed that the composite membranes improved mechanical properties as well as realized release of CeO NPs. We then applied the composite membranes to study in rat cranial defect models. Micro-CT and histopathological evaluations revealed that nanofibrous membranes with CeO NPs further accelerated new bone formation. Those exciting results demonstrated that CeO NPs and porous membrane contributed to osteogenic ability, and CeO NPs contained electrospun membrane may be a promising candidate material for periodontal bone regeneration.