These data suggest that Reypolysaccharide A has neuroprotective effects and improves cognitive impairment after cerebral ischemia by inhibiting ferroptosis and activating the PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathways, and these findings also provide valuable insights into the pathogenesis and therapeutic targets of ischemic stroke. Here, GPX4 is linked to brain ischemia.