Both aspartame (ASP) and monosodium glutamate (MSG) are added to many food stuffs, hence any meal may contain both of them, so their harmful effects should be studied together. Evidences of ASP nephrotoxic effect have increased; however, little information is available about nephrotoxicity of MSG. This study assessed the nephrotoxic effects of ASP & MSG administered either individually or in-combination. Forty eight male adult albino rats were divided into eight equal groups: negative control; positive control; ASP-treated; MSG-treated; “ASP&MSG”-treated; ASP-recovery; MSG-recovery and “ASP&MSG”-recovery. A single daily dose of ASP (250mg/kg) and MSG (4g/kg) were given orally according to the study regimen. The present study documented nephrotoxic effects of ASP and MSG evidenced by a significant increase in serum urea, creatinine and tissue malondialdehyde levels; a significant decrease in tissue reduced glutathione level; and renal structural damages detected in all treated groups. The worst findings were detected in “ASP+MSG”-treated group. Partial improvement in the renal histopathological and biochemical results was detected in all recovery groups.