This study aimed to evaluate the protective effects of rutin against monosodium glutamate (MSG)-induced nephrotoxicity through an integrated biochemical and histological approach. A total of 24 adult male rats (120–150 g) were randomly assigned to four groups (n=6): a control group (CONT) receiving no treatment, a rutin-treated group (RUT) administered 150 mg/kg rutin orally for 30 days, an MSG-exposed group (MG) given 60 mg/kg MSG daily for 30 days, and a co-treatment group (RUT+MG) receiving rutin followed by MSG at the same doses and duration. Body weight and kidney weight were recorded, and kidney function markers (urea, creatinine, and uric acid) were assessed. Oxidative stress markers, including glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA), were measured alongside inflammatory cytokines (TNF-α and IL-1β). Histological evaluation was performed using hematoxylin and eosin (H&E) staining. The results showed that MSG exposure significantly increased kidney weight, urea, creatinine, and uric acid levels, while also reducing GSH levels and antioxidant enzyme activities (SOD and CAT), with a concurrent rise in lipid peroxidation (MDA). Inflammatory markers TNF-α and IL-1β were also elevated in the MSG group. Histological examination revealed severe renal alterations, including glomerular shrinkage, tubular degeneration, and interstitial hemorrhage. However, co-administration of rutin markedly mitigated these changes by restoring kidney function markers, enhancing antioxidant defenses, reducing inflammation, and preserving normal renal histo-architecture. These findings suggest that rutin exerts significant nephroprotective effects against MSG-induced toxicity, demonstrating its potential therapeutic role in preventing kidney damage associated with dietary toxins.