Abamectin (ABM) is a common agricultural pesticide and veterinary anthelmintic drug. It can discharge from the sites of application to aquatic systems via surface run-off or spray drift, causing harmful effects to aquatic organisms. The present study investigated the protective effect of dietary quercetin supplementation on hemato-biochemical parameters and hepato-renal oxidative stress biomarkers in Nile tilapia (Oreochromis niloticus) exposed to a sublethal dose of ABM. Fish were allocated into six equal groups. The first group was kept as a control group. The second and third groups (Q400, and Q800) were fed diets supplemented with two quercetin levels (400 and 800 mg/kg diet), respectively. The fourth group (ABM) was intoxicated with 20.73 µg/L of ABM. The fifth and sixth groups (ABM + Q400, and ABM + Q800) were fed diet supplemented with two quercetin levels (400 and 800 mg/kg diet) and simultaneously intoxicated with ABM for 60 days. The results showed that ABM significantly decreased RBCs, hemoglobin content, hematocrit, total protein, albumin levels, and acetylcholinesterase activity activities compared to the control. Meanwhile, ABM significantly increased white blood cells, glucose, total lipids, cholesterol, and alanine and aspartate aminotransferase activities. Liver and kidney levels of lipid peroxidation was significantly increased, while hepato-renal antioxidant biomarkers (reduced glutathione, super oxide dismutase, catalase, and total antioxidant capacity) were significantly decreased upon ABM exposure. On the other hand, quercetin dietary supplementation improved the hemato-biochemical alterations and alleviated oxidative stress induced by ABM exposure. Fish supplemented with quercetin at a level of 800 mg/kg diet showed better alleviating effects against ABM compared to 400 mg/kg diet. Based on these study findings, we suggest that quercetin dietary supplementation (800 mg/kg) offered direct protection against ABM-induced physiological disturbance and oxidative stress in Nile tilapia.