The present experiment aimed to investigate anti-oxidant and hepatoprotective possibilities of lycopene (LYC) versus hepatic biochemical alterations induced by administration of monosodium glutamate (MSG). Rats were classified into five groups; Group I- (control), Group II- (MSG  15 mg/kg ), Group III- (MSG 35 mg/kg), Group IV- (MSG 15 mg/kg + LYC), Group V- (MSG 35 mg/kg + LYC). Our results demonstrated that MSG administration at both doses (15, 35 mg/kg /day) for 30 days induced hepatic toxicity as indicated with elevated hepatic enzyme leakage, oxidative stress, and hepatic histopathological deterioration comparing to control group. On the contrary, supplementation of LYC (10 mg/kg /day) pre- MSG administration for 10 days and co-administration with MSG for 30 days partially restored hepatic enzymes and elevated the anti-oxidant enzyme activities via reducing hepatic enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, reduced glutathione (GSH) level, in line with decreased malondialdehyde (MDA), and transforming growth factor beta1 (TGF-β1). As well as, lycopene administration improved hepatic architecture comparing to MSG. Taken together, the present results summarize that lycopene administration showed hepatoprotective effects versus monosodium glutamate promoted hepatic toxicity and thus can be considered as a novel hepatoprotective medication in clinic after being valid