Cerebral Ischemia-Reperfusion Injury ( CIRI ) is a key pathological link in the deterioration of neurological function after stroke. Its mechanism is closely related to oxidative stress and inflammatory response, and ultimately leads to severe neuronal damage. In recent years, the nuclear factor E2-related factor 2 / heme oxygenase-1 ( Nrf2 / HO-1 ) signaling pathway, which mediates endogenous protective effects, has received extensive attention. This pathway plays a central role in maintaining cellular redox homeostasis by regulating antioxidant, anti-inflammatory and anti-apoptotic processes. The purpose of this paper is to explore the activation mechanism and multi-directional protective effect of Nrf2 / HO-1 signaling pathway in CIRI, and to analyze the therapeutic potential of targeting this pathway based on this, so as to provide theoretical basis for the development of new neuroprotective drugs, in order to optimize clinical treatment strategies and improve the prognosis of patients.