Previous studies have found that intracorporal short-chain fatty acids (SCFAs), as the main metabolites of the gut microbiota, play important roles in the intestinal physiology and immune function. Along with the in-depth study of the brain-gut axis, the attention to the roles of SCFAs in central nervous system (CNS) has been raised. It has been found that SCFAs function in CNS diseases by regulating inflammatory response, neuronal apoptosis, oxidative stress, the integrity of the blood-brain barrier (BBB) and so on. Here, the changes, the effects and the mechanisms of different SCFA as individual or mixture in different CNS diseases were summarized. It is expected to lead to increased interest in SCFAs studies as an important regulator in CNS diseases and provide feasible suggestions based on SCFAs for the therapy of CNS diseases in the future.