The present study recorded a good trial for using orange peel as a natural additive to enhance the growth, the physiological, biochemical, and immunity measurements of the mono-sex Nile tilapia. Orange peel additive, 2% dried powder,  2% oil extraction, and 2% mixture of them (1:1); diet 1, diet 2, and diet 3, respectively, were used for feeding three test groups of fish besides to the control (0% additive). The best growth performance, feed utilization, and blood measurements were recorded for the three treated groups especially for those fed diet 3, which contained the mixture when compared to the control. Orange peel additive increased (p < 0.05) body protein and plasma total protein, while blood enzymes activity, lipid content, and cholesterol were decreased (p < 0.05). Immunological blood parameters (IgG & IgM) were enhanced for fish fed the additive. The present results determined that the immune response system was improved for fish fed the forms of orange peel.