This study investigated the effect of using a natural dietary supplement of Crataegus Sinaica (CS) to mitigate the negative impacts of waterborne acrylamide (ACR) on the health and performance of freshwater fish, African catfish (Clarias gariepinus). For this aim, 270 fish were divided into six groups (45 fish/group). Three groups were kept in non-contaminated water and fed a non-fortified basal diet, 1% CS, and 2% CS. The other three groups were exposed to ACR (26.6 mg/L water) and fed a basal diet, 1% CS, and 2% CS. After 60 days, the growth performance, liver and kidney function, stress indicators, oxidative stress indices, immunological response, vital tissue architecture, and resistance to Aeromonas sobria have been evaluated. Results indicated that CS dietary supplementation (1% and 2% CS) significantly counteracted ACR-induced reduced growth and survival. Furthermore, both CS dietary supplementation significantly balanced the ACR-induced leukopenia, anemia, hypoalbuminemia, hypoglobulinemia, and hypoproteinemia. Likewise, 1% and 2% CS addition to the ACR-exposed fish diets significantly reduced the ACR-induced increase in serum enzymes, bilirubin, renal damage products, hyperglycemia, and cortisol. Instead, the ACR-evoked depletion of antioxidant (glutathione peroxidase, superoxide dismutase, catalase, and reduced glutathione) and innate immune (lysozyme, complement3, and nitric oxide) components were significantly restored by both CS dietary supplementation. Besides, the ACR-induced pathological alterations in hepatic, renal, and splenic tissues were considerably lessened by CS. Besides, the reduced disease resistance of ACR-exposed fish was restored when challenged with A.sobria in a fish-fed 1% and 2% CS-fortified diet. Noteworthy, the inclusion of 2% CS produced better results than 1%. Overall, feeding C. gariepinus a diet supplemented with 2% CS significantly improved the fish's overall health, growth, and disease resistance, despite the ACR water pollution that consequently would sustain aquaculture.