The purpose of the current study was to assess the effect of dietary supplements of either aqueous (AE) or ethanolic (EE) (Juniperus communis) leaf extracts on growth performance, intestinal health, hemato-biochemical indices, antioxidant, inflammation cytokine responses, and resistances against infection in Nile tilapia, Oreochromis niloticus. Fish groups were controlled with no extract (J1) and fed diets (J2, J3, J4, and J5) containing 1.0 and 2.0 g/kg aqueous and ethanolic extract for 60 days. Fish were given an intraperitoneal injection (IP) of Aeromonas hydrophila for 10 days after the feeding trial; then, the fish mortality was recorded. Growth, feed efficiency, and activity of endogenous enzymes (lipase, trypsin, chymotrypsin, and amylase) were significantly improved in all dietary J. communis groups, especially in J5, compared to other groups. Also, J5 showed the highest absorption area, muscularis, goblet cells, villi width, and fewer gut bacterial counts than the other groups. In addition, the J4 and J5 groups of tilapia fish exhibited a significant increase in the levels of total protein, serum albumin, globulin, hemoglobin, white blood cells, and hematocrit (P< 0.05), as well as a significant decrease in the levels of serum alanine, aspartate aminotransferases, glucose, and cholesterol compared to the J1 groups. Moreover, the J4 and J5 fish showed a significant decline in the levels of MDA with improvements in antioxidant (SOD, CAT, and GPX) and immunological (lysozyme, immunoglobulin M, and complement C3) indices compared to the J1 group. Fish in J4 and J5 exhibited downregulated levels of il-8, il-10, il-1β, tnf-α, ifn-γ, and hsp70 genes compared to other groups. In contrast, hepatic catalase (cat), superoxide dismutase (sod), and interleukin (il-10) gene expressions were upregulated. The lowest fish mortality after the bacterial challenge was recorded in the J5 group. These findings suggest that 2.0 g/kg feed ethanolic extract of J. communis-fed Tilapia fish fingerlings improved their growth and intestinal health, boosted their immune systems and antioxidant responses, and increased their resistance to A. hydrophila.