Monosodium glutamate (MSG) is a common seasoning and flavor booster found in nearly every processed product. MSG induces oxidative stress along with degenerative changes in the hepatic and renal cells. This study aims to evaluate the protective effects of rutin(RT) and Moringa oleifera(MOE) extract against MSG-induced hepatotoxicity in rats. Forty adult male albino rats were randomly divided into four groups. The control group (CNT) received no treatment. The second group received MSG orally (60 mg/kg/day) for 30 days. The third and fourth groups were pretreated with RT (150 mg/kg/day) and MOE (500 mg/kg/day), respectively, for 30 days, followed by oral administration of MSG (60 mg/kg/day) for an additional 30 days, two hours after the RT or MOE dosage. The study assesses whether RT and MOE can reduce liver damage by leveraging their antioxidant, anti-inflammatory, and anti-apoptotic properties. This is evaluated through various biochemicals, histological, and molecular markers associated with oxidative stress, inflammation, and apoptosis in liver tissues. The results indicated that MSG induces organ dysfunction (AST and ALT levels), oxidative stress (GSH, SOD, CAT, GPx, GR, and NO), inflammation (IL-1 beta and TNF-alpha), histological alterations (H&E, PAS, Sirius red COX-2, and iNOS stains), and ultra-structural abnormalities of hepatocytes. The authors found that RT and MOE significantly mitigate MSG-induced liver damage in rats. Treatment with RT and MOE reduced oxidative stress, inflammatory responses, and apoptosis markers while enhancing antioxidant defenses, suggesting that both RT and MOE have therapeutic potential in preventing MSG-related liver toxicity due to their strong antioxidant and anti-inflammatory effects.