Stroke is a leading cause of death and permanent disability in adults worldwide. Advanced glycation endproducts (AGEs) are known to be increased in several chronic diseases and induce inflammation and protein crosslinking. The current study was designed to investigate the protective effect of benfotiamine, perindopril (at a sub-hypotensive dose), and alagebrium on experimentally induced stroke in mice. All drugs were administered for 9 days starting one week before 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 behavior tests and the reduction in brain infarction. This was associated with normalization of the levels of receptor for advanced glycation end products (RAGE) and its soluble form sRAGE that were changed following MCAO. In addition, benfotiamine, perindopril and alagebrium corrected the upregulation in the downstream effectors TNF-α and VCAM-1. The results of the current study represent a new indication for benfotiamine, perindopril, alagebrium in the management of ischemic stroke.