The occurrence of pathogenic bacteria, Aeromonas hydrophila, in farm‐raised fish requires urgent attention. Continuous and indiscriminate use of antibiotics as growth promoters and disease control agents in aquaculture have been discouraged because of the risk of development of antibiotic‐resistant bacterial strains. There is steady interest in the use of botanicals, such as clove, Eugenia caryophyllata, buds extract (ECBE), as alternatives. Hence, the present study evaluated the effect of dietary ECBE supplementation on the growth performance, physiological, antioxidant, and immunity biomarkers of African catfish, Clarias gariepinus. Fish (11.7 ± 0.5 g) were fed diets containing 0.0 (control), 5.0, 10.0, or 15.0 g ECBE/kg diet up to apparent satiation twice daily for 12 weeks. After the feeding trial, fish from each treatment were challenged with A. hydrophila infection by intraperitoneal injection and kept under observation for 14 days to record any abnormal clinical signs and daily mortality. The results demonstrated that fish performance and feed intake were significantly enhanced with increasing ECBE levels, and its optimum level is 15 g/kg diet. Further, the dietary ECBE increased significantly the intestinal villi length/width and absorption area in a dose‐dependent manner. There are significant progressive increases in the values of red blood cells, hemoglobin, hematocrit, white blood cells, platelets, lymphocytes, and heterocytes, while monocytes, eosinophil, and basophils decreased significantly due to dietary ECBE in a dose‐dependent manner. Highest glucose, cholesterol, total protein, globulin, and albumin‐globulin ratios, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, and creatinine values were found in fish fed 15 g ECBE/kg diets, while lowest values were recorded in fish fed the control diet. Despite the high AST and ALT values, no visible lesions or damage were observed in the liver cells of fish fed ECBE‐enriched diets. In addition, the inclusion of ECBE in fish diets enhanced the antioxidant and immunity capacity. Fish mortality after the bacterial challenge was higher in fish fed the control diet (82.3%) than those fed ECBE‐enriched diets. The lowest fish mortality was observed in fish fed the 15 ECBE/kg diet (4.7%) [Correction added on 16 November 2018: this section has been revised for clarity.].