Myelin oligodendrocyte glycoprotein (MOG) peptide, a truncated form of MOG located on the extracellular myelin sheath surface, interacts with antigen serotype HLA-DR2 to mitigate effects of ischemic stroke induced by middle cerebral artery occlusion (MCAO) in mice. In female mice, it notably reduces cortical and striatal infarct volumes, lessens sensorimotor deficits as observed in tube- and corner turn tests, enhances engagement with novel odors, and prolongs the duration of cage mate-directed vocalizations, without exhibiting similar outcomes in male mice.