The present invention discloses the combined treatment of memantine (N-methyl-D-aspartate receptor antagonist) and tea polyphenol (an antioxidant and anti-inflammatory agent) is more effective (synergistic) in neuroprotection than either memantine or tea polyphenol alone in mouse excitotoxic injury. These findings provide useful information about the potential application of memantine and tea polyphenols in preventing or treating clinical excitotoxic injury such as brain trauma, brain ischemia, epilepsy, and Alzheimer's disease.