The present study was conducted to investigate the effects of Ziziphus mauritiana leaf powder (ZLP) on growth performance, intestinal histomorphology and growth-related gene expression of Nile tilapia (Oreochromis niloticus). ZLP was incorporated into the basal diet at 5, 10 and 20 g per kg diets (w/w) and fed to fish for 12 weeks. The obtained results revealed significantly (P <.05) improved average body weight, weight gain percentage, feed intake, feed efficiency ratio, protein efficiency ratio and apparent protein utilization in fish fed ZLP as compared to fish fed ZLP free diet with the highest being in fish fed 10 g per kg diet. The highest carcass total protein and the lowest moisture and lipid contents were observed in fish fed ZLP at 20 g/kg as compared to the control, while the lowest ash content was observed in fish fed ZLP at 10 g/kg. Serum ion Na+ and Ca++ significantly increased (P˂0.05) in all groups fed with ZLP compared to the control group, while an increase in the serum K+ ion concentration was recorded at 5 and 10 g ZLP fed groups. Significant upregulations in insulin-like growth factor and ghrelin gene expression in fish fed ZLP were recorded (P <.05). The stomach showed an increase in the thickness of the gastric mucosa and muscularis in all treated groups with the highest values in 10 g/kg fed group. The intestinal mucosal folds, heights, widths, area and perimeter of the villi and thickness of muscular layers were significantly (P <.05) higher in groups fed with ZLP, which was confirmed by using scanning electron microscopy.Thus, ZLP can be used effectively in tilapia diets for improving the growth and intestinal health. © 2019 Elsevier B.V.