Background: In Africa, neurodegenerative diseases in the elderly have become a major health concern due to the increase in live expectancy. Glutamate mediated neurotoxicity is involved in neurodegenerative diseases such as Ischemia, Epilepsy, Alzheimer's and Parkinson diseases. Plants with antioxidant properties are reported to protect vital organs against glutamate toxicity. This study aims to assess the effect of Dichrocephala integrifolia against monosodium glutamatemediated neurotoxicity and oxidative stress. Methodology: The decoction prepared from the leaves of Dichrocephala integrifolia was evaluated against monosodium glutamate-induced neurotoxicity in mice. The animals were grouped in seven groups of 6 animals each. The animals received daily; distilled water (p.o) for the distilled water and the negative control groups, one of the four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o) for the tests groups and memantine (20 mg/kg p.o) for the positive control group. Monosodium glutamate (2.5 g/kg ip) was injected daily to animals except those of the normal control group all the seven days of the experimentation. Animals were observed for aggressiveness, locomotor and forepaws muscle grip activities 30 min after monosodium injections. Brain reduced glutathione and malondialdehyde levels were also assessed following the behavioral tests on day 8. Results: The decoction of Dichrocephala integrifolia at the doses of 87.5 and 175 mg/kg significantly (p<0.01) inhibited the aggressiveness of monosodium treated mice, significantly (p<0.01) counteracted the reduction in locomotor and forepaws muscle grip capacity induced by monosodium glutamate. Furthermore, the decreases in reduced glutathione level and increases in lipid peroxidation level induced by monosodium glutamate were significantly (p<0.001) reversed by Dichrocephala integrifolia at the doses of 87.5 and 175 mg/kg. Conclusion:The results of this study reveal that Dichrocephala integrifolia is a medicinal plant that protects the brain against monosodium glutamate-mediated neurotoxicity. This can explain why this plant is intensively used in folk medicine in Cameroon to prevent and treat some central nervous system illnesses.