Immunostimulant phytogenic feed additives are given great concern for improving fish health, growth, immune responses, and resistance to diseases. This research investigated the impact of dietary propolis (PRO), turmeric (TUR), and their combination on the growth, hematology, antioxidant-immune responses, and their regulating genes in Nile tilapia (Oreochromis niloticus) during Edwardsiella tarda challenge. For 8 weeks, a total number of 320 fish (20.70 ± 0.14 g) were allocated into four groups at random, each with eight replicates (10 fish each). The first group (1st) was given the basal diet (control) with out any supplements. The 2nd, 3rd, and 4th groups were supplemented with 1% PRO, 1% TUR, and the mixture (1%PRO + 1%TUR), respectively. The experimental groups were challenged intraperitoneally with E. tarda at a dose of 0.1 mL (1 × 105 CFU) at the termi nation of the feeding trial, and the fish survival was estimated for an additional 7 days. The results demonstrated that fish-fed diets supplemented with PRO and/or TUR showed higher body weight, condition factor, specific growth rate, feed intake, and feed efficiency utiliza tion than the control group (P < 0.05). The hematological, protein profile, and antioxidant immune (total antioxidant capacity, lysozymes, and IgM) parameters were substantially improved in the challenged fish fed on PRO and/or TUR diets compared to the challenged non-fed fish. The lipid profile and malondialdehyde were substantially decreased in the challenged fish fed on PRO and/or TUR diets compared to the challenged non-fed group.