This experiment was designed to estimate the effect of different levels of dietary protein with the addition of Aqua-Max Plus® (as a feed additive) on growth performance, feed utilization, the chemical composition of the whole fish body, and physiological responses of mono-sex Nile tilapia, Oreochromis niloticus. Six hundred of mono-sex Nile tilapia fingerlings (at average initial bodyweight 52.64 ± 5.2 g) were distributed randomly to five treatments. Experimental diets contain different levels of dietary crude protein 21, 23, 25, 27% (referred to No. T1, T2, T3, and T4, respectively) and that were compared to the control diet contains 25% without adding Aqua-Max Plus® (T0). Results revealed that the increasing dietary protein in diets leads to an improvement in growth performance and hematological parameters as well as total protein, albumin, and globulin concentrations in blood serum. Fish fed on a diet containing 21% protein (T1) recorded the lowest values of growth performance, feed efficiency, and hematological parameters. The addition of Aqua-Max Plus® to diets containing 23% (T2) and 25% (T3) crude protein enhanced growth performance and feed efficiency parameters compared to the control diet. Protein content was significantly improved, whereas fat, ash and EC contents were reduced by increasing the dietary protein. The addition of Aqua-Max Plus® to the experimental diets had no significant effect on serum biochemical parameters. Finally, the addition of Aqua-Max Plus® in the Nile tilapia diets improve the nutritional values of low protein diets, and it is a way to reduce the cost of fish feed.