Cerebral ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This vascular obstruction and the subsequent decrease in the cerebral blood flow results in immediate drop in the neurological activity that might end in death of brain tissue or cerebral infarction / ischemic stroke. In the present study, the effects of Nicotine and Simvastatin and their combinational effect on cerebral ischemia-induced cognitive impairment in rats were investigated. The animals were pre-treated with Nicotine and Simvastatin for a period of 10 days. Cerebral ischemia was induced by Bilateral Common Carotid Artery Occlusion (BCCAO) of rats for 30 minutes followed by reperfusion. The treatment was continued for another week after surgery. To evaluate the learning and memory parameters, Rectangular maze test, Morris Water maze test, locomotor activity tests were conducted. Catalase activity and DPPH assay were also assessed. Donepezil was used as standard drug. This study demonstrates the neuroprotective effect of Nicotine and Simvastatin on improving the cognitive function and by increasing the free radical scavaging activity. The memory enhancing capacity of the drugs was very significant when compared to disease control (p<0.001).