Vitis amurensis, Aralia cordata, and Glycyrrhizae radix have been widely used as oriental medicinal plants in Korea, China and Japan and found to possess anti-oxidative and anti-inflammatory activities. A previous study demonstrated a protection of an ethanol extract (SSB) of a mixture of three medicinal plants of Vitis amurensis, Aralia cordata, and Glycyrrhizae radix against β amyloid protein-induced memory impairment. The current study was conducted to investigate the neuroprotective effect of SSB against ischemiainduced brain injury. Transient focal cerebral ischemia was induced by 2 hr middle cerebral artery occlusion followed by 24 hr reperfusion (MCAO/reperfusion) in rats. Oral administration of SSB (5, 10 and 25 mg/kg) 30 min before and 1 h after MCAO, and 1 h after reperfusion reduced MCAO/ reperfusion-induced brain infarct and edema formation. SSB also inhibited development of behavioral disabilities in MCAO/reperfusion-treated rats. Exposure of cultured cortical neurons to 500 μM glutamate for 12 hr resulted in neuronal cell death. SSB (1-10 μg/mL) inhibited glutamateinduced neuronal death, elevation of intracellular calcium concentration ([Ca2+]i), and generation of reactive oxygen species (ROS). These results suggest that the neuroprotective effect of SSB against ischemia-induced brain damage might be associated with its anti-excitotoxic activity and that SSB may have a therapeutic role for prevention of neurodegeneration in stroke.