Ferroptosis, an iron-dependent form of programmed cell death, is closely linked to ischemic stroke (IS). This review summarizes the mechanisms of ferroptosis in IS, focusing on iron metabolism, lipid peroxidation, and glutathione and amino acid metabolism. Ferroptosis is triggered by iron overload, lipid peroxidation, and disrupted antioxidant systems, leading to neuronal and microglial damage. Key pathways include the extrinsic (transporter-dependent) and intrinsic (enzyme-regulated) pathways. Iron metabolism involves transporters like transferrin and ferroportin, while lipid peroxidation is catalyzed by enzymes such as ACSL4 and LOX. Glutathione metabolism, particularly through GPX4, plays a critical role in preventing lipid peroxidation and ferroptosis. Ferroptosis contributes to IS pathology by increasing ROS production, disrupting the blood-brain barrier, and promoting neuroinflammation. Therapeutic targets include GPX4, system Xc⁻, ACSL4, and LOX. Compounds such as selenium, curcumin, and ferrostatin-1 analogs have shown potential in inhibiting ferroptosis. Additionally, Nrf2 signaling and the regulation of SLC7A11 are crucial for modulating ferroptosis. The review highlights the importance of targeting ferroptosis for IS treatment, emphasizing the need for further research to develop effective therapies. Despite progress, challenges remain in understanding the complex mechanisms of ferroptosis and translating findings into clinical applications.Ferroptosis, an iron-dependent form of programmed cell death, is closely linked to ischemic stroke (IS). This review summarizes the mechanisms of ferroptosis in IS, focusing on iron metabolism, lipid peroxidation, and glutathione and amino acid metabolism. Ferroptosis is triggered by iron overload, lipid peroxidation, and disrupted antioxidant systems, leading to neuronal and microglial damage. Key pathways include the extrinsic (transporter-dependent) and intrinsic (enzyme-regulated) pathways. Iron metabolism involves transporters like transferrin and ferroportin, while lipid peroxidation is catalyzed by enzymes such as ACSL4 and LOX. Glutathione metabolism, particularly through GPX4, plays a critical role in preventing lipid peroxidation and ferroptosis. Ferroptosis contributes to IS pathology by increasing ROS production, disrupting the blood-brain barrier, and promoting neuroinflammation. Therapeutic targets include GPX4, system Xc⁻, ACSL4, and LOX. Compounds such as selenium, curcumin, and ferrostatin-1 analogs have shown potential in inhibiting ferroptosis. Additionally, Nrf2 signaling and the regulation of SLC7A11 are crucial for modulating ferroptosis. The review highlights the importance of targeting ferroptosis for IS treatment, emphasizing the need for further research to develop effective therapies. Despite progress, challenges remain in understanding the complex mechanisms of ferroptosis and translating findings into clinical applications.