This experiment was designed to assess the effect of alternative plant protein sources (soya bean meal (SBM), corn gluten meal (CGM), distiller dried grains (DDG)), with or without spirulina (Arthrospira platensis) supplementation, on growth, feed utilization, body composition, histological (liver and intestine) changes of Nile tilapia, Oreochromis niloticus. A total of 180 Nile tilapia, O. niloticus, fingerlings (3.78 ± 0.02 g) were assigned to six treatments (three replicates each, 10 fish each), and were stocked in 100 L glass aquarium. Fish were fed with six experimental diets using SBM, CGM, and DDG with or without spirulina supplementation at dose of 0.5%. The feeding experiment lasted for 84 days. The results indicated that tilapia fed on SBM based diet with or without spirulina supplementation have significantly improved growth performance, survival, feed conversion ratio and nutrient utilization compared to other treatments. Serum protein profile showed an increase of significant globulin with SBM and A. platensis supplemented diets. Moreover, the SBM based diet alone or supplemented with A. platensis improved both liver histopathological featuring and glycogen contents, and increased intestinal villi length and area of absorption values. It is recommended that SBM should be used as plant protein source, supplemented with 5 kg-1 diet spirulina in Nile tilapia diet.