The present study evaluated the effects of dietary onion (Allium cepa)powder and its extracts on growth, blood biochemical parameters, non‐specific immune parameters and potential disease resistance against pathogenic Aeromonas hydrophila infection in Oreochromis niloticus. Fish formulated diets containing onion powder (1% or 0.5%) or onion alcoholic extracts (1% or 0.5%). At the end of the experiment, the weight gain and specific growth rate were significantly increased than control. Besides, red blood cells (RBCs) and haemoglobin (Hb) showed a significant increase with insignificant changes of leukocytic cells count (WBCs), triglycerides, creatinine and uric acid levels. Results showed significant increase of total protein and albumin, and significant enhancement of innate immune response including serum globulins, serum antiprotease, lysozyme activities, myeloperoxidase content and the phagocytic index compared with the control group. Meanwhile feeding on onion increased superoxide dismutase, catalase activities and glutathione‐S‐transferase but significantly decreased hepatic peroxidase. The cumulative mortality of O. niloticus injected with A. hydrophila exhibited relatively low mortality levels in all onion supplemented groups. The relative per cent survivals were 100%, 100%, 80% and 70% in 1% onion powder, 0.5% powder, 1% extract and 0.5% extract groups, respectively, compared with control (60%). Additionally, there was a significant increase in relative immune gene expressions of interleukin 1‐beta (IL‐1β), and transforming growth factor‐beta 1 (TGF‐β1) in head kidney tissues of treated groups than the control. These results confirm the anti‐inflammatory and antioxidative activities of dietary onion with its beneficial effects on growth performance and disease resistance against A. hydrophila in O. niloticus.