The growing aquaculture sector demands the development of sustainable and cost-effective feed ingredients. An 12-week feeding trial was conducted to determine the effect of supplementation of plant-based diets of Ulva lactuca (Ulva) with exogenous enzymes (mono or multi-enzyme complex) and yeast on growth performance ,feed utilization and biochemical parameters of Nile tilapia (Oreochromis niloticus). Six isonitrogenous and isocaloric diets were formulated to supply 28% protein and 425 kcal/100 g diets. The treatments were: (1) positive control diet (fishmeal-based), (2) negative control diet (Ulva based diet), (3) Ulva based diet + 1.50 g phytase/kg, (4) Ulva based diet + 1.50 g xylanase/kg and (5) Ulva based diet + 3 g yeast /kg (6) Ulva based diet + 1.50 g multi-enzyme complex /kg. The fish that were fed the fishmeal-based diet and the Ulva diets supplemented with different enzymes or yeast had significantly better growth performance and survival rate values compared to those fed Ulva alone. The highest values of blood parameters (Hb, RBCs, and Ht) were observed in fish fed the multi-enzyme supplemented diet. There were no significant differences in total protein serum and albumin among the experimental treatments. The results suggest that supplementation of Ulva based diet with enzymes or yeast can improve the nutrient utilization and growth performance of Nile tilapia while remaining cost-effective.