Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Advanced glycation endproducts (AGEs) are known to be increased in several chronic diseases and induce inflammation and protein intercalation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (r-TPA). The current study was designed to investigate the protective effect of benfotiamine (70 mg/kg/day), perindopril (2 mg/kg/day) and alagebrium (2 mg/kg/day) on experimentally-induced ischemic brain damage. All drugs were administered daily for one week before and 2 days after middle cerebral artery occlusion (MCAO). Benfotiamine, perindopril and alagebrium ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in initiation of walking test and improvement of the deteriorated brain histology. This was associated with normalization of the level of AGEs that was increased following MCAO. The result of the current study represent a new indication for benfotiamine, perindopril, alagebrium in the management of ischemic stroke.