Objective This study aims to investigate the regulatory effects of calcitonin gene-related peptide (CGRP) on Nod-like receptor protein 3 (NLRP3) and interleukin-1β (IL-1β) to promote osteoblast differentiation.Methods Different concentrations of CGRP (0, 10, 30, 100 ng•mL-1) were added to mouse osteoblasts in vitro. The mRNA and protein expression levels of both NLRP3 and IL-1β were examined using Real-time polymerase chain reaction and Western blot, respectively. Moreover, the concentrations of IL-1β protein and intracellular reactive oxygen species (ROS) were detected using enzyme-linked immunosorbent assay and flow cytometry, respectively. The osteogenic differentiation of mouse osteoblasts was identified through alizarin red staining.Results The protein and mRNA expression levels of both NLRP3 and IL-1βsignificantly decreased (PConclusion CGRP promotes osteoblast differentiation by inhibiting the expression of inflammatory factors.