Protein lactylation is a recently discovered post-translational modification, and its neuroprotective effect in cerebral ischemia-reperfusion injury has garnered increasing attention. Cerebral ischemia-reperfusion injury is a complex pathological process that occurs following reperfusion therapy after ischemic stroke, involving oxidative stress and inflammatory responses. This article reviews the neuroprotective mechanisms of protein lactylation in cerebral ischemia-reperfusion injury and highlights recent research progress. Lactate molecules can covalently bind to lysine residues and affect the function and activity of proteins, thus playing significant roles in cell metabolism, gene expression regulation, and cell signaling. Research has indicated that protein lactylation exerts neuroprotective effects by regulating inflammatory and oxidative stress responses, helping to reduce neuronal damage and apoptosis. In-depth studies of the biological functions of protein lactylation and its mechanism of action in cerebral ischemia-reperfusion injury not only aid in elucidating the pathophysiological mechanisms underlying cerebral ischemia-reperfusion injury, but also provide potential targets and theoretical basis for the development of new therapeutic drugs for cerebral ischemia-reperfusion injury.