Actinidia arguta (Actinidiaceae) has been reported to have several pharmacological effects such as anti-inflammatory, anti-allergic, and anti-oxidant activities. The present study investigated the protective activity of an ethanol extract from the leaf and stem of A. arguta against glutamate-induced neurotoxicity using cultured rat cortical neurons. Exposure of cultured cortical neurons to 500 uM glutamate for 12 h triggered neuronal cell death. A. arguta inhibited glutamate-induced neuronal death and apoptosis, which were measured by a 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining, respectively. The increase of pro-apoptotic proteins, Bax and c-caspase-3, in glutamate-treated neurons was significantly inhibited by treatment with A. arguta. A. arguta also inhibited 500 uM glutamate-induced elevation of intracellular calcium concentration ([Ca2+]i) and reactive oxygen species (ROS) generation, which were measured by fluorescent dyes, Fluo-4 AM and H2DCF-DA, respectively. These results suggest that A. arguta may prevent glutamate-induced apoptotic neuronal death by inhibiting [Ca2+]i elevation and ROS generation and, therefore, may have a therapeutic role for the prevention of neurodegeneration in cerebral ischemic diseases.