Background The glycogen synthase kinase 3β (GSK-3β) is a multifunctional Ser/Thr kinase involved in a variety of metabolic processes, and is abundant in the central nervous system. Recent studies revealed that the of modulation of GSK-3β is associated with numerous pathophysiologic processes. Objective we analysized and summarized the role of modulation of GSK-3β activity in neuroprotection with its related mechanism. Content This article described the basic structure and modulation of GSK-3β, the neuroprotection of GSK-3β inhibitor against cerebral ischemia reperfusion injury and related mechanism. Trend The nueroprotective effect of GSK-3β inhibitor against cerebral ischemia reperfusion injury demonstrated the therapeutic prospective of development of isoform-specific inhibitors or gene silencing.