Peroxynitrite involvement has been implicated in the neuronal damage. In the present study, we have investigated the neuroprotective effects of peroxynitrite decomposition catalyst (FeTMPyP) on global cerebral ischemia. Global cerebral ischemia-reperfusion (IR) injury was produced by 5 min occlusion of both common carotid arteries followed by reperfusion of 96 h in the adult male Mongolian gerbils. The extent of injury was assessed behaviorally by measuring neurological functions, locomotor activity, passive avoidance test and by histopathological evaluation of extent of damage to CA1 hippocampal pyramidal region. FeTMPyP (1 and 3 mg kg −1, i.p., administered 30 min prior to ischemia) treatment improved the neurological functions, reduced the hyperlocomotion and memory impairment in IR challenged gerbils. The loss of neurons from the pyramidal layer of the CA1 region caused by global IR injury was attenuated with FeTMPyP. FeTMPyP also inhibited lipid peroxidation as evident from reduction in brain malondialdehyde levels. These results suggest that peroxynitrite decomposition catalyst may be effective neuroprotective agent for global cerebral ischemia.