A feeding study was conduct to investigate the effect of dietary supplementation of xylanase on growth performance, feed utilization, digestive enzymes, proximate composition, hematological and serum biochemical parameters of Nile tilapia, Oreochromis niloticus fingerlings fed plant-based diets for 70 days. Three isonitrogenous (293 g kg^–1 crude protein) and isocaloric (18.42 MJ kg^–1 gross energy) diets were formulated. Each diet was supplemented with xylanase at levels; 0 (control), 0.5 and 1 g kg^–1 diet. After 70 days, the highest weight gain, specific growth rate, protein efficiency ratio, protein productive value, fat retention, energy retention, and the best feed conversion ratio were recorded in fish fed either 0.5 or 1 g xylanase kg^–1 diet. As well as, the addition of xylanase up to 0.5 g kg^–1 diet increases the activity of lipase, amylase, and trypsin. The addition of xylanase significantly improved hemoglobin, hematocrit, red blood cells, white blood cells, total protein, albumin, and globulin compared with the control diet. On the other hand, the addition of xylanase increased low-density lipoprotein cholesterol. The highest values of growth hormone and phosphorus were observed in fish fed diets supplemented with 0.5 g xylanase kg^–1 diet. Based on the obtained findings, it could be conclude that the useful using of xylanase as feed additive up to 0.5 g kg^–1 diet for significantly enhancement the growth performance, feed utilization, endogenous enzyme activity, and physiological responses of O. niloticus.