Aquaculture is one of the most important food production industries, both economically and in terms of food security for the world's growing population. O. niloticus is the second largest freshwater species that is used as a bio-indicator. Zinc oxide nanoparticles (ZnO NPs) are commonly eluted from industries and excessively accumulate in aquatic environments highly vulnerable to fish that induce alterations in tissues. C. forskaolii Vahl is an edible annual herb with high therapeutic value. In the present study, we synthesized green nanoparticles using C. forskaolii Vahl acts as a reducing, stabilizing, and capping agent which is an alternative to the conventional chemical method. Further, the comparative evaluation of chemical and green synthesized ZnO NPs exposure on acute toxicity (96hrs), sublethal toxicity (28 days) and histological alterations were examined in the gills, liver and muscles of female O. niloticus. The results of acute toxicity of female O. niloticus exposed to chemical and green synthesized ZnO nanoparticles were identified to be 2.533 mg/L and 4.210 mg/L. In addition, sublethal toxicity was also found after 28days exposure to chemical and green synthesized ZnO nanoparticles in female O. niloticus is 0.168 mg/L, 0.253 mg/L, 0.506 mg/L followed by 0.280 mg/L, 0.421 mg/L and 0.842 mg/L. Furtherly, chemically synthesized ZnO NPs exhibited severe histological alterations such as congestion in gills, congestion of the central vein and hepatic sinusoid with fatty changes of hepatocytes in the liver and congested blood vessels in muscle than in green synthesized ZnO NPs. In conclusion, the present study determined that green synthesized ZnO NPs using C. forskaolii Vahl reduce the damages caused by the nanoparticles to aquatic foremost organism fishes compared to the chemical method.