O-GlcNAcylation is a post-translational protein modification, which can reversibly attach n-acetylglucosamine to the serine/threonine terminal and it is widely found in cells. This paper focuses on the mechanism of protein modification and the role of O-GlcNAcylation in ischemic injury diseases. O-GlcNAcylation mediated mitochondrial dynamic changes, apoptosis, endoplasmic reticulum stress, cell energy metabolism, autophagy and oxidative stress, which can effectively prevent and relieve cell damage caused by ischemia and hypoxia. The present research results suggest that O-GlcNAcylation plays a key role in ischemic injury diseases and provides new preventive measures and therapeutic ideas for the clinical treatment of ischemic injury diseases.