In this study, we prepared macrophage-derived exosomes laden with heptapeptide (Hep) as a dynamin-related protein-1 (Drp1)–fission 1 (Fis1) peptide inhibitor P110 to alleviate cerebral ischemia–reperfusion injury by reducing mitochondrial Drp1/Fis1 interaction-mediated astrocytic mitochondrial disorder and promoting the transfer of astrocyte-derived healthy mitochondria into neurons. This evidence concerns the gene FIS1 and Cerebral ischemia.