Background: Although monosodium glutamate (MSG) is commonly used as a food additive, the application of higher doses or prolonged uses significantly leads to accumulations in living cells and finally produces cellular toxicity. Persea Americana (avocado) has recently gained substantial popularity and is often marketed as a “superfood" because of its unique nutritional composition, antioxidant content, and biochemical profile. Aim: To evaluate the potential ameliorative role of avocado fruit extract against MSG-induced nephrotoxicity in pregnant rats and their offspring. Thirty-two (24 females and 8 males) albino rats were used in this study. After an acclimatization period of two weeks; the animals were mated, and the pregnant rats were randomly divided into four groups; control (G1), avocado (G2): they were supplemented with 50 mg/kg b.w. of avocado fruit extract, MSG (G3): they were given 3g / kg b.w. of MSG, every other day, and MSG &Avocado (G4): they were given an oral dose of MSG alternatively with avocado fruit extract. At the end of weaning, the female rats and their offspring were sacrificed and the blood was collected and the kidneys were excised to evaluate the renal biochemical and histopathological, and immunohistochemical investigations. Results: In MSG-treated mothers' rats, the renal cortical sections displayed severe histopathological lesions including little renal corpuscles, atrophied glomeruli, and relatively wide Bowman^'s space. However, the offspring displayed mild renal histopathological lesions compared with their mothers. The immunohistochemical results revealed strong PCNA and Bax expression in the renal tissues of MSG-exposed mother rats and their offspring if compared with the control.  Furthermore, the mean percentage value of positively expressed cells for caspase-3 appeared significantly higher in the renal cells of MSG-induced mother's rats and their offspring if compared with the control. Additionally, the levels of serum antioxidants (SOD&CAT) and potassium ions appeared significantly lowered while the level of MDA, urea, and creatinine appeared significantly higher if compared with the control.  Co-supplementation of avocado fruit extract to MSG-induced mothers rats and their pups successfully alleviated the histopathological, immune-histo-chemical, apoptotic as well as biochemical changes caused by MSG.  Conclusion: Avocado fruit extract has a powerful ameliorative role against MSG-induced renal toxicity in mother rats and their offspring.