The use of medicinal plants and probiotics in fish feeding improve the nutritional value of a diet, enhance growth performance, quality of fish flesh and improve immunological parameters. Onion is used as a medicinal plant where it is an antibiotic and an antioxidant and has anticancer properties. Mustard used as feed ingredient to make supplemental aqua feed in fish industries. Probiotics Saccharomyces cerevisiae can play an effective role in the diet improved feed efficiency of fish. About 400 Nile tilapia were divided into equal 4 groups, the 1st group was fed a basal diet (control group), 1.5g /100g Species mixture (onion slices and Mustard seeds) to the 2nd group, 1 gm Saccharomyces cervisae/100gm diet to the 3rd group while 4th group fed spices mixture and probiotics (synergestic). Results revealed fish fed on supplemented diet with species mixture and probiotics had better growth performance, phagocytic and lyozyme activity, IgM level and survival of Nile tilabia against Aeromonas hydrophila compared to fish fed on unsupplemented diets.