Ischemic brain is highly vulnerable to free radicals mediated secondary neuronal damage especially mitochondrial dysfunctions. Present study investigated the neuroprotective effect of S-allyl L-cysteine (SAC), a water soluble compound from garlic, against cerebral ischemia/reperfusion (I/R)-induced mitochondrial dysfunctions in hippocampus (HIP). We used transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia. SAC (300 mg/kg) was given twice intraperitoneally: 15 min pre-occlusion and 2 h post-occlusion at the time of reperfusion. SAC significantly restored ATP content and the activity of mitochondrial respiratory complexes in SAC treated group which were severely altered in MCAO group. A marked decrease in calcium swelling was observed as a result of SAC treatment. Western blot analysis showed a marked decrease in cytochrome c release as a result of SAC treatment. The status of mitochondrial glutathione (GSH) and glucose 6-phosphate dehydrogenase (G6-PD) was restored by SAC treatment with a significant decrease in mitochondrial lipid peroxidation (LPO), protein carbonyl (PC) and H2O2 content. SAC significantly improved neurological deficits assessed by different scoring methods as compared to MCAO group. Also, the brain edema was significantly reduced. The findings of this study suggest the ability of SAC in functional preservation of ischemic neurovascular units and its therapeutic relevance in the treatment of ischemic stroke.