ABSTRACT: The influence of herbicides causes health and economic loss, which requires innovative solutions to sustain the aquaculture industry. In this regard, dietary isatis is included in Nile tilapia diets to relieve atrazine (ATZ)-induced growth retardation, hepato-renal dysfunction, and oxidative stress. The first and second groups offered the control diet (control), while the third and fourth groups offered the isatis supplemented diet (1%). Meantime, half of the water was replaced and mixed with ATZ (1.39 mg/L) in the second and fourth groups for 30 days. The group of fish delivered isatis had significantly enhanced FBW, WG, and SGR, while fish intoxicated with ATZ had meaningfully impaired growth behavior (p < 0.05). Further, the FCR was improved by isatis, and ATZ resulted in the worst FCR among the groups. Interestingly fish fed isatis and exposed with ATZ (88.89%) had a higher survival rate than fish exposed with ATZ without isatis feeding, and both are lower than the control (97.78%) (p < 0.05). The histological structure in the isatis-treated groups showed distinguished enhancement and branching of the intestinal villi. The intestine of ATZ-treated fish revealed damage and inflammatory cell infiltration in the intestinal mucosa with separation of lining epithelium. Generally, fish fed isatis and intoxicated with ATZ had lower uric acid, urea, creatinine, ALT, and AST and higher total protein, globulin, and albumin than fish exposed with ATZ without feeding with isatis (p < 0.05). Markedly, fish-fed isatis had the highest SOD, CAT, GPx, and the lowest MDA level compared to the other groups (p < 0.05). Meanwhile, fish exposed with ATZ had the worst SOD, CAT, GPx, and the highest MDA level compared to the other groups (p < 0.05). In summary, dietary isatis relieved ATZ induced growth retardation, hepato-renal dysfunction, and oxidative stress in Nile tilapia.