Nile tilapia Juveniles (19.50 ± 0.5 g) were fed on a basal diet (control group (CTR)) and a diet supplemented with 1 g (ASP) per kg diet for 12 weeks. Fish were then subjected to different salinity levels (0, 10, 15, and 20 practical salinity units (psu)) for another 15 days. Two-way ANOVA analysis revealed that the individual effects of ASP in Nile tilapia exposed to salinity levels presented a significant decrease ( < 0.05) in values of haemato-biochemical indices (such as glucose, cortisol, alanine transaminase, aspartate transaminase, and malondialdehyde) compared to those in the CTR group exposed to the same salinity levels. Moreover, significant increases ( < 0.05) of blood protein profile (albumin, globulin, and total protein), non-specific immune responses (lysozyme activity, phagocytic activity, and phagocytic index), and antioxidant enzymes activities (glutathione peroxidase, catalase, and superoxide dismutase) were observed in ASP-supplemented groups. Interestingly, there was significant ( < 0.05) downregulation of the mRNA expression values of heat shock protein 70 and interferon-gamma genes, alongside upregulation of the mRNA expression values of interleukin 1 beta and interleukin 8 genes, in the hepatic tissues of Nile tilapia in ASP-supplemented groups exposed to different salinities compared to those in the CTR group exposed to the same salinity levels. Taken together, these findings supported the potential efficacy of dietary supplementation with ASP in alleviating salinity stress-induced haemato-biochemical alterations, immune suppression, and oxidative stress in the exposed Nile tilapia.