Red ginseng has long been used as a traditional medicine in many East Asian countries including Korea. It is known to exhibit various pharmacological effects, including anti-oxidant, anti-cancer, anti-stress and anti-diabetes activities. To further explore its actions, the present study evaluated effects of Korean red ginseng (KRG) extract on neuronal injury induced by various types of insults using primary cultured rat cortical cells. KRG extract inhibited neuronal damage and generation of intracellular reactive oxygen species (ROS) induced by excitatory amino acids, such as glutamate and N -methyl-D-aspartate (NMDA), or by A_β(25–35). To elucidate possible mechanism(s) by which KRG extract exerts neuroprotective action, its effects on apoptosis and apoptosis-related signaling molecules in neurons were assessed. KRG extract markedly increased phosphorylation of Bad at Ser 112 and inhibited Bax expression and caspase 3 activity. It also inhibited DNA fragmentation induced by NMDA or A_β(25–35). These results indicate that KRG extract protects cultured neurons from excitotoxicity and A_β(25–35)-induced toxicity through inhibition of ROS generation and apoptotic cell death. In addition, KRG extract inhibited β-secretase activity, implying that it may reduce A_β peptide formation. Taken together, these findings suggest that KRG extract may be beneficial for the prevention and/or treatment of neurodegenerative disorders including Alzheimer’s disease.