Monosodium glutamate (MSG) is a flavor enhancer. Oxidative neurotoxicity of MSG is well established. This study explored the therapeutic effect of red clover’s (RC) extract against MSG–induced neurodegeneration. HPLC-analysis revealed that formononetin, genistein, daidzein and biochanin A are the major isoflavones in RC’s extract. Four equal groups of male rats were used: control group, MSG-treated group, MSG plus RC-treated group and RC-treated group. The gene expression of iNOS, TNF-α, Cox-2 and p53 were evaluated in the brain extract using RT-PCR. The histological and electron microscopic examinations as well as the cholinergic function, the neurotransmitters and the oxidative status were also assessed. The MSG significantly up regulated the expression levels of iNOS, TNF-α, Cox-2 and p53. The activity of acetyl cholinesterase (AChE), the monoamine neurotransmitters and the oxidative status as well as the histological and electron microscopic examinations confirmed the MSG-induced neurodegeneration. The administration of RC plus MSG diminished the expression of the inflammatory cytokines, the activity of AChE and the levels of monoamine neurotransmitters. RC also ameliorated the oxidative stress and the histological and the electron microscopic alterations. Accordingly, the present study provides an insight on the antioxidative and anti-inflammatory potentials of RC’s extract as neuroprotective agent.