Background: Monosodium glutamate is widely used as flavor enhancer/food additive. Many studies confirmed toxicity of monosodium glutamate even if in low concentrations especially in hepatic and renal organs. Therefore, our study aimed to examine ameliorative role of Nano-cerium oxide and L-arginine and their combination on the hepatic and renal toxicity induced by monosodium glutamate. Materials and Methods: Fifty mice were divided into five groups; 1st group served as control group; 2nd group treated oral with monosodium glutamate; animals of the 3rd group were administrated with monosodium glutamate and L-arginine. The 4th group was treated with monosodium glutamate and Nano-cerium oxide; and mice of the 5th group were treated with monosodium glutamate, L-arginine and Nano-cerium oxide. After 14 days, hepatic and renal tissues were removed for histological and histomorphometrical examinations Results: Histological examination revealed hepatic and renal damages for animals treated with monosodium glutamate as well as highly significant declining of DNA content compared to control group. Administration of Nano-cerium oxide or L-argentine alone induced ameliorations of the hepatic and renal injuries induced by administration of monosodium glutamate but some pathological alterations still present. It also caused moderate improvement in the DNA content but still not reaches to normal value. Combined administration of Nano-cerium oxide and L-arginine caused marked ameliorations of the hepatic and renal changes induced by monosodium glutamate. Conclusions:The combined uses of L-arginine and Nano-cerium oxide more effective in preventing the hepatic and renal toxicity induced by monosodium glutamate in male albino rats than when they uses separately.