Severe periodontitis frequently leads to irreversible degradation of alveolar bone. Periodontal regeneration techniques hold immense potential in reconstructing alveolar bone post periodontal diseases. Schwann cells (SCs) play a critical role in supporting, maintaining, and regenerating periodontal tissues, with SC-derived exosomes (SC-EXO) exhibiting cell homing and tissue repair capabilities. Nevertheless, the specific role of SC-EXO in periodontal bone regeneration remains unknown. To address the issue, we treated human periodontal ligament cells (hPDLCs) with SC-EXO and observed a notable increase in cell proliferation, and osteogenic and neurogenic differentiation. Moreover, SC-EXO stimulated the expression of angiogenic factors in vascular endothelial cells. In a rat model of periodontal bone defects, SC-EXO facilitated the recruitment of endogenous cells, regulated neural and vascular neogenesis, and accelerated periodontal bone regeneration. This study successfully prepared SC-EXO, which effectively promotes periodontal bone regeneration by regulating the bone healing microenvironment, potentially offering a valuable strategy for periodontal tissue engineering.