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Stroke is one of the leading causes of death and permanent disability worldwide. Ischemic preconditioning (IPC) is an endogenous protective strategy, which has been reported to exhibit a significant neuroprotective effect in reducing the incidence of ischemic stroke. However, the underlying neuroprotective mechanisms of IPC remain elusive. An increased understanding of the pathogenic mechanisms of stroke and IPC serves to highlight the importance of metabolic reprogramming. In this review, we summarize the metabolic disorder and metabolic plasticity in the incidence and progression of ischemic stroke. We also elaborate how IPC fully mobilizes the metabolic reprogramming to maintain brain metabolic homeostasis, especially for energy and redox homeostasis, and finally protects brain function in the event of an ischemic stroke.