A 100- day study was conducted to evaluate the influence of two natural additives in the tilapia diet on growth, food performance and physiological conditions. Hence, six treated diets (30 % protein, 3000 k cal) were used; the control (0% additives) and diets1, 2 and 3, containing 1%, 2% & 3% dried mulberry leaves (ML), respectively. Whereas, diets 4, 5 and 6 contained 1%, 2% & 3% dried guava leaves (GL). Fish were stocked in ponds with 30 fish/ part (2.5 x 2 x 1.5 meters), and an initial average weight of 24 ± 0.5 g. The best bodyweight gain, specific growth rate, feed conversion ratio and protein efficiency ratio were recorded for the fish fed on diets 4 & 5, which contained 1% & 2% of guava additive. Whereas, fish fed on diet 1 with 1% mulberry leaves (p < 0.05) was rated the next, compared to fish fed on the control diet. The results revealed that the addition of guava leaves powder with levels 1% and 2 %, followed by 1% mulberry improved fish growth performance and feed utilization. In all fish treatments, the carcass composition data detected an increase in protein content accompanied by a decrease in fat percentage. Fish physiological measurements (plasma glucose, cholesterol and triglycerides) revealed that supplementing the Nile tilapia diets with the ML and GL showed a  significant decrease (p < 0.05) if compared with the control. An increase was recorded in the plasma total protein and globulin levels in all treated fish, compared to the control group, and accompanied with optimal liver enzymes activity. Hence, both ML and GL proved their beneficial impact on fish performance and nutrient utilization besides their role in enhancing the immune system of fish through vitamin C content in guava leaves that helps to maintain the health of blood vessels.