The genus Ocimum (family Lamiaceae) has been revered for its diverse biological activities. Various species have been used traditionally to treat CNS disorders and are proven to have neuroprotective effect that is often attributed to their significant antioxidant activity. Ocimum kilimandscharicum (Karpoora Thulasi), a prominent member of this genus is reported to have marked antioxidant activity but its neuroprotective potential has not been explored. Thus, present study was designed to evaluate the cerebroprotective effect of O. kilimandscharicum leaf extract (OKLE) in mice against ischemia reperfusion (I-R) induced brain injury. Bilateral common carotid artery occlusion (BCCAO) for 15min followed by 24h reperfusion was used to induce brain damage in Swiss Albino mice. Animals were treated with OKLE (200 and 400mg/kg, po) once daily for 7days after I-R. Morris water maze and elevated plus maze tests were used to assess long and short term memory while neurological severity score was used to determine motor coordination. Histopathological evaluation (TTC staining) along with brain biochemical parameters (TBARS, reduced GSH and SOD activity) were determined to outline neuroprotective mechanism of OKLE. I-R resulted in marked cognitive impairments, motor incoordination in mice, significant brain damage and increased oxidative stress. Treatment with OKLE produced functional recovery in mice which is manifested by improved memory and motor coordination; reduced cerebral infarct size and brain oxidative stress (TBARS levels) and elevated endogenous antioxidants (reduced GSH and SOD activity). In addition, OKLE showed DPPH radical scavenging and reducing power in-vitro. These results show that O. kilimandscharicum mitigated the neurodegenerative changed induced by I-R in mice probably due to its antioxidant activity.