A feeding trial was conducted to investigate the effect of dietary incorporation of turmeric powder (TP), Curcuma longa and clove bud powder (CBP), Syzygium aromaticum on growth, antioxidant, and immune response of Nile tilapia, Oreochromis niloticus, as well as its resistance to pathogenic bacteria, Proteus mirabilis. Fish (27.56 ± 0.15 g) were randomly allocated into four groups in triplicates. The first (control) group was fed basal without any feed addition. The second and third groups were fed on a basal diet enriched with 0.5% TP and 3% CBP, respectively, and the fourth group was fed on a basal diet enriched with a mixture of TP and CBP for 6 weeks. After the 6 weeks of feeding, fish were intraperitoneally injected with P. mirabilis, and mortalities were recorded up to 14 days. Fish growth parameters were significantly improved in all groups fed TP and/or CBP enriched diets as compared to the control group. The immune response of fish that were fed on dietary TP+CBP mixture followed by TP then CBP before and after bacterial challenge showed significant augmentation in terms of lysozyme activity, nitric oxide, and total protein especially total globulin, as well as the hepatic level of antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD) activities and reduced glutathione content (GSH)] over those of the control fish. The fish challenged with P. mirabilis showed the highest mortality rate and lowest relative percentage of survival; whereas the highest RPS was recorded in the fish fed TP+CBP mixture and TP (75%). Hence, TP and/or CBP could be used as a dietary additive to improve growth and immune response as well as to protect Nile tilapia against P. mirabilis infection.