Lowering nanoparticles (NPs) toxicity before discharge into aquatic environments and employing agricultural waste materials for environmental sustainability are necessary nowadays. Since this has never been done, this work examines how green CuO NPs treated with rice husk (RH) as a bio-adsorbent may be safer for Nile tilapia (Oreochromis niloticus) than chemically manufactured ones. So, five groups of fish were randomly placed in glass aquaria. One group was a control, and four groups received 50 mg/L green and chemically produced CuO NPs (GS and CS) with and without RH for 24, 48, and 96 h. RH was collected from all groups, and the results showed GS-CuO NPs had a greater adsorptive capacity than CS-CuO NPs after all time intervals. After analyzing fish indicators in all groups compared to the control, higher Cu bioaccumulation was exhibited in the liver and gills. The liver and gills showed elevated levels of glutathione peroxidase (GPx), catalase (CAT), and thiobarbituric acid reactive substances (TBARS), while the levels of glutathione reduced (GSH) were significantly lower. In addition, Cu exposure impaired liver and gill histology. Finally, our results indicated that using RH as an adsorbent for CuO NPs after their green synthesis instead of chemical synthesis before they enter the aquatic environment can enhance the overall health of fish and environmental sustainability.