Excessive ammonia accumulation poses significant risks to aquaculture, potentially compromising the performance and productivity of aquatic species. The investigation aimed to determine the impacts of dietary supplementation with Opuntia littoralis cladodes (OLCP) at 0% (OLCP-0), 0.5% (OLCP-1), 1% (OLCP-2), and 2% (OLCP-3) on growth performance, haematological, immuno-biochemical indices, digestive enzyme activity, and antioxidant responses. However, a study was conducted on the Nile tilapia (O. niloticus) (25.49±0.25g) for sixty days (pre-phase). After that, fish were exposed to ammonia stress (0.5mg/ L) for 24 hours (post-phase). The findings indicated that dietary OLCP, particularly at 1% and 2% levels, significantly stimulated growth and enhanced protease, amylase, and lipase activities. Data revealed improved haematological parameters and immunological markers (complement C3, lysozyme activity, and total immunoglobulin) with increased OLCP levels. However, the exposure to ammonia caused a general reduction in these parameters, and the 2% OLCP group maintained the highest improved levels.  The higher concentrations of OLCP diets before and after ammonia-induced stress significantly enhanced the antioxidant defenses, especially in the 2% OLCP group. Additionally, OLCP supplementation reduced malondialdehyde (MDA) levels and leukocyte counts. Overall, the results suggested that prickly pear cladodes, can improve the growth, immune function, and antioxidant response of tilapia fish diets, especially in the 2% OLCP group, while effectively reducing the adverse impacts of ammonia exposure on their immuno-biochemical and haematological indices.