Antioxidants have been the focus of studies for developing neuroprotective agents to be used in the therapy for stroke, which is an acute and progressive neurodegenerative disorder and is the second leading cause of death throughout the world. In fact, many herbal antioxidants have been developed in in vitro and in vivo experiments and some of these have been tested in clinical studies of stroke. Embelia ribes have been reported to have antioxidant and antidiabetic effects. In addition to these effects, this study was designed to investigate the neuroprotective effect of ethanolic extract of E. ribes Burm fruits on middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Male Wistar albino rats were fed ethanolic E. ribes extract (100 and 200 mg/kg body weight; p.o.) for 30 days. After 30 days of feeding, all animals were anaesthetized with chloral hydrate (400 mg/kg, i.p.). The right middle cerebral artery was occluded with a 4–0 suture for 2 h. The suture was removed after 2 h to allow reperfusion injury. Ischemia followed by reperfusion in ischemic group rats significantly (P<0.001) reduced the grip strength activity and non-enzymatic (reduced glutathione, GSH) and enzymatic [glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)] antioxidant levels in hippocampus and frontal cortex compared to sham-operated rats. Further, serum lactate dehydrogenase (LDH) and thiobarbituric acid reactive substance (TBARS) levels in hippocampus and frontal cortex were significantly increased in ischemic group compared to sham-operated rats. Furthermore, ethanolic E. ribes extracts pretreatment significantly (P<0.001) increased the grip strength activity, and GSH, GPx, GR and GST levels in hippocampus and frontal cortex with significant decrease in LDH levels in serum and TBARS levels in hippocampus and frontal cortex compared to MCAO + vehicle group rats. The data from this study suggest that chronic treatment with ethanolic E. ribes extract enhances the antioxidant defense against MCAO-induced focal cerebral ischemia in rats and exhibits neuroprotective activity.