Aquatic plants are potent antioxidants that might promote health and reduced oxidative damage induced by a variety of ecological pollutants in aquatic organisms. The privileges of dietary Thalassodendron Ciliatum intervention were assessed in Nile tilapia (Oreochromis niloticus) pre- and post-acute ammonia exposure. A total of 160 healthy male juveniles (weighing 12.4 ± 0.01 g) were allocated randomly into four equal groups (each group containing four replicates). The feeding trial lasted for 8 weeks; the first group served as a control (fed a basal diet), while, the remaining three groups were fed diets supplemented with 1, 3 or 5% T. ciliatum extract (TCE1%, TCE3% and TCE5% respectively). By the end of the feeding trial, all fish groups had been exposed to a 6-h acute ammonia exposure with 5 mg TAN per Liter, relying on pH level and water temperature degree. Prior to the ammonia toxicity test, all performance data indicated that a low dosage of TCE (1 or 3%) resulted in significant improvements (P > 0.01 or 0.001). Meanwhile, fish assigned TCE5%-rich diets reported the highest levels of crude protein and lowest lipid percentages when compared to the control group. Furthermore, fish administered a high dose of TCE had significantly (P < 0.001) higher serum protein constituents, interleukin-1 (IL-1), immunoglobulins M and G, and lysozyme levels and reduced liver enzyme and total necrosis factor-2α contents pre- and post-ammonia exposure. Pre- and post-ammonia toxicity, TCE incorporation into fish diet significantly (P < 0.001) promoted the antioxidant activity along with stimulating the transcription of the IL-8, GSH and CAT genes. Moreover, the TCE5% fish group showed higher effectiveness in mitigating the ammonia toxicity risks on the gill structure and displayed apparently normal structure. Finally, although it may be suggested that including small quantities of TCE (1 to 3%) into fish diets might promote growth under conventional aquaculture systems, higher TCE levels (5%) were proven to be essential in triggering immunological and antioxidant responses under intensive culture systems.