<p>Studies have shown that the prognosis of dental implant treatment in patients with diabetes is not as good as that in the non-diabetes population. The nerve plays a crucial role in bone metabolism, but the role and the mechanism of peripheral nerves in regulating peri-implant osteogenesis under Type 2 diabetes mellitus (T2DM) situation remains unclear. In this study, it was shown that high glucose-stimulated Schwann cells (SCs) inhibited peri-implant osteogenesis via their exosomes. SCs-derived exosomes were analyzed for their miRNA cargo, identifying miR-15b-5p as significantly downregulated in high glucose conditions. T2DM rats and patients exhibited decreased miR-15b-5p expression, correlating with impaired bone microarchitecture. Luciferase assays and Western blotting confirmed <i>TXNIP</i> as a direct miR-15b-5p target, implicating its involvement in ROS signaling and inflammation-related osteogenesis suppression. Furthermore, normal SCs exosomes improved bone parameters around dental implants in T2DM rats. These findings underscore the therapeutic potential of miR-15b-5p and normal SCs exosomes in mitigating poor peri-implant bone regeneration of T2DM patients, offering insights into the molecular mechanisms of peripheral nerves governing bone regeneration in diabetic conditions.</p> Graphical Abstract <p></p>