Background: Stroke is ranked on top of the persistent ailments associated with the brain. The incidence of ischemic stroke is rapidly rising along with intensified mortality as well as permanent disability conditions. However, tissue plasminogen activator (tissue-type plasminogen activator) is the only FDA-approved treatment for the treatment of stroke with decreased success rate. Eriocitrin, a flavonoid compound of Citrus limon with incredible therapeutic values, was active in the current investigation to explore the neuroprotective capability in arterial occlusion-provoked cerebral ischemic reperfusion injury (CIRI) in mouse replica. Materials and Methods: The neurological defects were considered through the standard scoring method and the expression status of apoptotic proteins, i.e., nuclear factor kappa B (NF-ƙB), caspase-3, and caspase-9, was examined via western blotting test. The expression of neuronal nitric oxide synthase (nNOS) was scrutinized through real-time polymerase chain reaction and standard ELISA kits were employed to examine the status of the proinflammatory markers. Results: The arterial occlusion provoked cerebral ischemic animals displayed the severely elevated status of inflammatory markers namely interleukin-6 (IL-6), IL-1β and tumor necrosis factor α, and the expression statuses of apoptotic proteins, as well as nNOS, were also uplifted while comparing to the sham subjected animals. Amazingly, eriocitrin (100 mg/kg) treatment revealed the declined inflammatory markers level, besides, the expression patterns of apoptotic proteins and nNOS were also reduced noticeably in the cerebral ischemic-reperfusion-operated animals. Conclusion: The novel findings of this investigation were demonstrated that the Eriocitrin delivered an astounding neuroprotection in the arterial occlusion-mediated CIRI in mouse replica, which possibly a promising neuroprotectant in cerebral ischemia.