Central nervous system diseases are major causes of global health loss and disability, and effective, targeted treatments are still lacking. Lactate, a key metabolic product of glycolysis, can regulate processes such as β-amyloid deposition, Tau protein phosphorylation, neuroinflammation, endothelial cell apoptosis, neuronal ferroptosis, microglial proliferation, and immune evasion of tumor cells through lactate metabolism and lactylation modifications, thereby contributing to the pathogenesis and progression of central nervous system diseases. Research has shown that exercise can exert a protective effect in central nervous system diseases by modulating lactate metabolism and lactylation modifications. This review summarizes the roles of lactate metabolism and lactylation modifications in central nervous system diseases, as well as the potential mechanisms by which exercise regulates lactate metabolism and lactylation modifications to improve these diseases, providing a theoretical basis for the beneficial effects of exercise on brain health.