To investigate protective effects and mechanism of grape seed proanthocyanidin (GSP) on H9c2 car-diomyocyte, CCK-8 assay was used to evaluate cell viability, Western-blot was used to evaluate the effects of GSP on apoptosis-related proteins (cleaved caspase-3, Bax and Bcl-2) and PI3K/Akt pathway-related pro-teins (p-PI3K, PI3K, p-Akt and Akt), and TUNEL and Hoechst 33258 stainings were used to evaluate the apoptosis of H9c2 cardiomyocytes. The results showed that GSP can prevent the cytotoxicity and apoptosis of H9c2 cardiomyocytes induced by H2O2. GSP decreased the expression of pro-apoptotic proteins cleaved cas-pase-3 and Bax, and increased the expression of anti-apoptotic protein Bcl-2. When GSP acted on H9c2 cells, the phosphorylation levels of PI3K and Akt increased, leading to activation of the PI3K/Akt signaling pathway. The experiments preliminarily demonstrated that GSP can inhibit H9c2 cardiomyocyte apoptosis induced by oxidative stress, and its mechanism of action may be related to PI3K/Akt signaling pathway ac-tivation.