Qing Nao Yi Zhi Fang (QNYZ), a traditional Chinese medicine, has been developed as a drug to be used for the prevention and treatment of vascular dementia. However, the mechanisms by which this drug affects vascular dementia remain unknown. We examined the effects of QNYZ serum on glutamate excitotoxicity in rat fetal cerebral neuronal cells in primary culture. Exposure of neuronal cells to glutamate leads to a decrease in the activities of cholinesterase, superoxide dismutase, and streptoavidin peroxidase, and an increase in lactate dehydrogenase release. These enzyme activities were restored to the levels in untreated cells by the addition of QNYZ serum. QNYZ serum suppressed the increased nitric oxide production induced by glutamate and prevented glutamate-mediated apoptosis. QNYZ serum also improved mitochondrial energy metabolism after glutamate exposure. These findings suggest that QNYZ has protective effects against glutamate-mediated excitotoxicity in neuronal cells during ischemic brain injury.