Objective This study aimed to observe the protective effect of calcitonin gene-related peptide (CGRP), as well as its potential mechanism, against oxidative damage in MC3T3-E1 osteoblasts. Methods 1) MC3T3-E1 osteoblasts were treated with different hydrogen peroxide (H2O2) concentrations (10-1, 10-2, 10-3, 10-4, and 10-5mol·L-1) for 12, 24, 36, and 48 h to build an oxidative damage model, to determine cell proliferation activity in each group by using CCK-8 assay, and to determine the optimal modeling concentration. MC3T3-E1 osteoblasts were pretreated for 1 h with different CGRP concentrations (10-6, 10-7, 10-8, 10-9, and 10-10mol·L-1) followed by treatment with H2O2(10-4mol·L-1). After 12, 24, 36, and 48 h, the CGRP expression and activity of osteoblasts were detected using the CCK-8 method to determine the optimal CGRP concentration that provides the best protective effect against oxidative damage. 2) Superoxide dismutase (SOD) activity, reactive oxygen species (ROS) content, and the levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 of the groups treated with CGRP, H2O2, CGRP+H2O2were determined. Results 1) Compared with the control group, treatment with 10-4mol·L-1H2O2significantly started to inhibite the proliferation of osteoblasts (P-4mol·L-1H2O2group, pretreatment with 10-8mol·L-1CGRP significantly increased the proliferation of osteoblasts (P2O2group, CGRP+H2O2group significantly increased the SOD activity (PPP2O2can cause oxidative damage to MC3T3-E1 osteoblasts, whereas CGRP exerts protective effect against oxidative damage in MC3T3-E1 osteoblasts.