Ischemic stroke remains a leading cause of global mortality and long-term disability, driven largely by oxidative stress, mitochondrial dysfunction, and inflammatory cascades. DJ-1 (PARK7), a redox-sensitive protein originally implicated in Parkinson's disease, has emerged as a critical neuroprotective regulator in cerebral ischemia. Oxidation of its cysteine-106 residue enables DJ-1 to stabilize mitochondrial function, suppress reactive oxygen species, and activate Nrf2-dependent antioxidant defenses. DJ-1 deficiency markedly exacerbates infarct size and neuronal vulnerability, whereas its activation confers robust neuroprotection. This review highlights DJ-1 as a promising redox-responsive therapeutic target for limiting ischemic brain injury.