Treatment with CSO significantly attenuated the ischemic stroke injury and blood–brain barrier (BBB) disruption; reduced iron accumulation, lipid peroxidation, and mitochondrial destruction; and regulated the key proteins of ferroptosis including GPX4, long‐chain acyl‐CoA synthetase 4 (ACSL4), transferrin (TF), TF receptor, SLC7A11 (xCT), heme oxygenase 1 (HO1), and ferritin heavy chin 1 (FTH1). Here, GPX4 is linked to ischemic stroke.