The present study was conducted to investigate the toxic effect of abamectin (ABM) and to evaluate the modulatory role of heat treated jojoba leaves extract (JLE) as feed additive in Oreochromis niloticus (O. niloticus) fish. 300 Nile tilapia fingerlings were randomly distributed in to 5 equal groups (4 replicates each). The first group (control) was fed on basal diet. The second group (ABM) was fed on basal diet and exposed to 1/10 of the 96 h LC50 of ABM (20.73 μg/L). The third (ABM + JLE0.5), the fourth (ABM + JLE1) and the fifth (ABM + JLE2) groups were exposed to ABM and fed on diet supplemented with 0.5, 1 and 2 g JLE/kg, respectively. ABM altered the water quality parameters by increasing the total ammonia and reducing the dissolved oxygen while JLE reversed these effects. Apart from feed conversion, ABM decreased the growth parameters of exposed fish when compared to control. These values were modulated in JLE exposed groups in a concentration dependent manner. ABM increased ALT and AST levels while JLE1 and JLE0.5 restored their levels to the control values, respectively. ABM altered the lipid profile of exposed fish while JLE2 restored total cholesterol to normal value. Reduced glutathione content was decreased by ABM and was restored to normal by JLE2. The highest level of lipid peroxidation (MDA) was recorded in ABM and ABM + JLE0.5 groups while JLE1 and JLE2 decreased the MDA level. The total antioxidant capacity was decreased by ABM while the highest value was recoded in both control and JLE0.5 groups. The level of IgG, IgA and C3 were decreased by ABM while its level was restored to normal by using JLE. Exposure of fish to ABM resulted in a significant increase in the nitric oxide level. ABM group had lower moisture and higher crude lipids in the whole-fish body than the supplemented groups. It could be concluded that dietary supplementation of JLE can positively attenuate the toxic effects of ABM on growth, immunity, physiological and antioxidant parameters thereby improving the general health condition and decreasing the mortality of O. niloticus. Additionally, the heat treatment attempted on the leaves could be considered as an eco-friendly method for detoxification.