Collectively, these findings suggest that EE may attenuate ferroptosis-related pathways possibly involving SIRT1/AKT/GSK3β-dependent glycogen metabolic remodeling, providing a novel metabolic perspective on EE-induced cerebroprotection and highlighting SIRT1-centered regulation of glycogen metabolism as a potential therapeutic target for ischemic stroke. Here, SIRT1 is linked to ischemic stroke.