The environmental effluents negatively affect the health and biochemical functions of tresterial and aquatic animals. It is crucial to ascertain the mechanisms of induction of adverse effects and applications of different natural and syenthetic antioxidants to mitigate the negative impacts in target and not target animals. Therefore, in this trial broccoli (Brassica oleracea) was used to ameleiorate the negative effects of zinc oxide nanoparticles in fish. Mono sex Nile tilapia (Tilapia niloticus), fish reared in different groups were treated with variable doses of zinc oxide nanoparticles alone (T1-T2) mg/kg feed and the fish of groups (T4-T6) were fed with variable doses of nanoparticles and broccoli in combinations for a total duration of 28 days in cemented tanks having 200L water. Tissues (kidneys and brain) were obtained at different intervals of experiment for estimation of oxidative stress, severity of histopathological lesions and antioxidant profile. Results showed that oxidative profile in term of ROS and TBARS escalated significantly (p<0.05), while antioxidants enzymatic parameters like superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were decreased significantly (p<0.05) in treated fish. The induction of oxidative stress and histo-architectural alterations were partially reduced in fish of groups (T4-T6). Various histo-architectural ailments in kidneys (atrophy and obliteration of renal tubule, nuclear hypertrophy, edema ceroid formation and deterioration of glomerulus) and in brain (edema, atrophy of neuron, microgliosis, neuronal degeneration, congestion and necrosis of neuron) were examined in treated fish. In conclusion, the findings of our trial unveiled that the supplementations of broccoli partially improved the antioxidant enzymes in tilapia by modifying the severity of inflammation.