"In this work, we studied the digestibility, growth, blood chemistry, and enzyme activity of Nile tilapia (Oreochromis niloticus) juveniles (0.95±0.18 g) using different animal (fish silage meal, whey meal, bovine blood meal, and red crab meal) and plant (extruded bean, extruded chickpea meal, coconut paste, Jatropha curcas meal, and chickpea meal) dietary byproducts. Nine isocaloric diets (321.92±9.10 kcal g−1) were evaluated for 60 days. The highest digestibility of crude protein values for animal and plant sources were obtained for the whey (93.6) and extruded bean meal (90.5) diets, respectively. The final body weight was higher for the red crab and extruded chickpea meal diets, meanwhile the fish silage and red crab byproducts obtained the highest protein efficiency ratio. Hematocrit was similar among the diets of each byproduct source and presented correlation with growth parameters. The highest glucose, cholesterol, and triglyceride values were obtained for fish silage (138.0, 260.5, and 389.0 mg dL−1, respectively) and whey meal (174.5, 242.3, and 284.0 mg dL−1, respectively) groups. A positive correlation was found between the digestibility of crude protein of ingredients and chymotrypsin activity. Oreochromis niloticus is able to better utilize fish silage, whey, extruded bean, and extruded chickpea byproducts, adjusting its digestive physiology. Such ingredients can be used for formulating cheaper and efficient tilapia diets."