This experiment was performed to verify the potential of dietary supplementation with bentonite, mannan-Oligosaccharide (MOS), organic selenium (OS) or vitamin C on reversing the harmful impacts resulting from lead (Pb) diet contamination in Nile tilapia (Oreochromis niloticus). One hundred and eighty tilapia fish were alienated into six groups fed on basal diet only, basal diet polluted with 50 ppm Pb, Pb polluted basal diet supplemented with 40 g bentonite, 50 mg vitamin C, 4 g MOS or 0.3 mg of organic selenium/kg diet for 16 weeks. The results revealed that fish fed diets polluted with Pb showed significantly (P < 0.01) impaired in growth performance indicators, hematological parameters, liver, and kidney by products. In contrast, a significant (P < 0.01) enhancement in the growth performance was noted with the tested feed additives with the highest level in MOS treated group followed by OS then bentonite and vitamin C. Also, fish groups fed diet fortified with the tested feed additives showed a significant (P < 0.05) enhancement in serum albumin, total protein, erythrocytes, and hemoglobin concentrations. Moreover, supplemented the contaminated diets with studied feed additives significantly (P < 0.001) reduces the Pb residuals in the fish body. Conclusively, supplementation of the fish diet with the tested feed additives could be a very useful strategy to combat the hazards of metal toxicity in fish.