As the organ with the highest demand for oxygen, the brain has a poor tolerance to ischemia and hypoxia. Despite severe ischemia/hypoxia induces the occurrence and development of various central nervous system (CNS) diseases, sublethal insult may induce strong protection against subsequent fatal injuries by improving tolerance. Searching for potential measures to improve brain ischemic/hypoxic is of great significance for treatment of ischemia/hypoxia related CNS diseases. Ischemic/hypoxic preconditioning (I/HPC) refers to the approach to give the body a short period of mild ischemic/hypoxic stimulus which can significantly improve the body's tolerance to subsequent more severe ischemia/hypoxia event. It has been extensively studied and been considered as an effective therapeutic strategy in CNS diseases. Its protective mechanisms involved multiple processes, such as activation of hypoxia signaling pathways, anti-inflammation, antioxidant stress, and autophagy induction, etc. As a strategy to induce endogenous neuroprotection, I/HPC has attracted extensive attention and become one of the research frontiers and hotspots in the field of neurotherapy. In this review, we discuss the basic and clinical research progress of I/HPC on CNS diseases, and summarize its mechanisms. Furthermore, we highlight the limitations and challenges of their translation from basic research to clinical application.