Ferritinophagy and ferroptosis are critical pathogenic mechanisms in cerebral ischemia-reperfusion injury (CIRI). Ferritinophagy, a selective autophagy process, regulates iron metabolism and can induce ferroptosis by releasing free iron. Ferroptosis, an iron-dependent form of cell death, is linked to lipid peroxidation and oxidative stress. NCOA4-mediated ferritinophagy plays a key role in regulating ferroptosis by modulating iron metabolism and ROS generation. Both processes are involved in the pathogenesis of CIRI, with iron metabolism and lipid metabolism being central to their mechanisms. Ferroptosis is regulated by the GPX4-centered antioxidant system and other pathways, including the FSP1-CoQ10, DHODH, and GCH1-BH4 pathways. Ferritinophagy is regulated by NCOA4, which interacts with FTH1 and is influenced by factors such as iron levels, autophagy, and hypoxia. Targeting ferritinophagy and ferroptosis offers potential therapeutic strategies for CIRI, including the use of iron chelators, antioxidants, and drugs that modulate NCOA4 or other key proteins. Traditional Chinese medicine and acupuncture have also shown promise in mitigating CIRI through various mechanisms, including reducing oxidative stress and inhibiting ferroptosis. Current research highlights the importance of understanding the regulatory mechanisms of ferritinophagy and ferroptosis in CIRI to develop effective treatments. Potential therapies include targeting NCOA4, using iron chelators, and modulating signaling pathways such as Nrf2, cGAS-STING, and others. Further studies are needed to elucidate the specific mechanisms and optimize therapeutic approaches for CIRI.Ferritinophagy and ferroptosis are critical pathogenic mechanisms in cerebral ischemia-reperfusion injury (CIRI). Ferritinophagy, a selective autophagy process, regulates iron metabolism and can induce ferroptosis by releasing free iron. Ferroptosis, an iron-dependent form of cell death, is linked to lipid peroxidation and oxidative stress. NCOA4-mediated ferritinophagy plays a key role in regulating ferroptosis by modulating iron metabolism and ROS generation. Both processes are involved in the pathogenesis of CIRI, with iron metabolism and lipid metabolism being central to their mechanisms. Ferroptosis is regulated by the GPX4-centered antioxidant system and other pathways, including the FSP1-CoQ10, DHODH, and GCH1-BH4 pathways. Ferritinophagy is regulated by NCOA4, which interacts with FTH1 and is influenced by factors such as iron levels, autophagy, and hypoxia. Targeting ferritinophagy and ferroptosis offers potential therapeutic strategies for CIRI, including the use of iron chelators, antioxidants, and drugs that modulate NCOA4 or other key proteins. Traditional Chinese medicine and acupuncture have also shown promise in mitigating CIRI through various mechanisms, including reducing oxidative stress and inhibiting ferroptosis. Current research highlights the importance of understanding the regulatory mechanisms of ferritinophagy and ferroptosis in CIRI to develop effective treatments. Potential therapies include targeting NCOA4, using iron chelators, and modulating signaling pathways such as Nrf2, cGAS-STING, and others. Further studies are needed to elucidate the specific mechanisms and optimize therapeutic approaches for CIRI.