Abstract: The main pathogenic mechanism of ischemic stroke-reperfusion injury is neuronal oxidative stress induced by aberrant increase in reactive oxygen species during the ischemic stroke-reperfusion process.Restoration of blood flow in cerebral tissue while inhibiting neuronal oxidative damage would be an effective way to treat ischemic stroke.Currently, the efficacy and application of clinical antioxidant drugs are greatly restricted by their low bioavailability, single mode of action, and serious side-effects.In recent years, nanomedicines have shown promising biological applications due to their controllable size and morphology and high surface modification, which are expected to break the bottleneck in the development of neuroprotective drugs for ischemic stroke.This review elucidates the mechanism of cerebral ischemia-reperfusion injury and summarizes the design and synthesis of antioxidant nanomedicines, their mechanism of action and application in reversing oxidative damage in neurons, which will provide a new strategy for the prevention and treatment of ischemic stroke.