The current investigation assessed the beneficial impacts of dietary sodium chloride (NaCl) on the growth performance, oxidant/antioxidant, and immune responses of Nile tilapia (Oreochromis niloticus) and its adaptability to different salinity levels. After acclimating the fish to the laboratory conditions for 2 weeks, the acclimated fish (10.5 ± 0.16 g) were randomly distributed into 25 110-L rectangular glass tanks (15 fish/tank) to represent five groups in five replicates. The fish were fed with experimental feeds fortified with 0.0 (control), 5, 10, 15, and 20 g NaCl/kg feed for 60 days. Following the nutritional experiment, fish of all groups were adapted to different salinity levels from 0 to 32 g /L for a further 3 weeks, during which fish mortality was recorded. Blood samples were taken after the feeding trial and at a salinity level of 24 g/L. Growth performance and hematological parameters (WBCs, RBCs, hemoglobin, and hematocrit), total protein, albumin, globulin, digestive enzymes, antioxidant activity, and immunity status were markedly improved with increased NaCl rates in the fish diets up to 10 g/kg feed, after which all previous parameters were declined. On the other hand, feeding fish on a diet containing 10 g NaCl/kg feed showed substantially lower levels of cortisol, glucose, cholesterol, triglycerides, aspartate transaminase (AST), alanine transaminase (ALT), and malondialdehyde (MDA). Exposing the control fish group to salinity stress (32 g/L) for 3 weeks markedly decreased their digestive enzyme activity, immunity status, and antioxidant response, along with significant increases in cortisol, glucose, cholesterol, triglycerides, AST, ALT, and MDA levels. Conversely, feeding fish on a diet containing 10 g NaCl/kg feed alleviated the negative impacts of salinity stress and helped fish to tolerate salinity stress up to 24 g/L.