Background: Monosodium Glutamate (MSG) is one of the most commonly used flavor-enhancing substances that may lead to neurological disorders. Objectives: The present work aimed to evaluate the role of L-ascorbic acid (AA) and -tocopherol (T) on the MSG-induced memory and neurobehavioral changes in rats. Methods: Thirty male Wistar albino rats were randomized into five equal groups: (1) control group, (2) MSG group received MSG (2mg/g BW) daily, (3) MSG+A group received MSG as in MSG group, and AA (100 mg/kg BW) daily, (4) MSG+T group received MSG as in MSG group, and T (600 mg/kg BW) twice weekly, and (5) MSG+AT group received MSG as in MSG group, AA as in MSG+A group, and T as in MSG+T group. After 3 weeks, neurobehavioral changes were assessed by open field test and Y maze. Oxidative stress markers were estimated, and immunohistochemistry was studied in hippocampal region. Results: MSG resulted in impairment of memory and induction of anxiety, with increased hippocampal malondialdehyde and decreased superoxide dismutase and glutathione peroxidase. Treatment with AA or T improved all the measured biochemical parameters, and the MSG-induced hippocampal degenerative changes, with decreased glial fibrillary acidic protein (GFAP) and synaptophysin expression. Combined administration of both vitamins was more effective in amelioration of MSG-induced impairments rather than taking AA or T alone. Conclusion: Both AA and T exhibit protective effects against neurobehavioral changes, oxidative stress and hippocampal degenerative changes induced by MSG toxicity, with more potent efficacy of their combination.