The effects of supplementing diets with acetone extract (1% w/w) from four medicinal plants (Bermuda grass Cynodon dactylon, H(1), beal Aegle marmelos, H(2), winter cherry Withania somnifera, H(3) and ginger Zingiber officinale, H(4)) on growth, the non-specific immune response and ability to resist pathogen infection in tilapia Oreochromis mossambicus were assessed. In addition, the antimicrobial properties of the extract were assessed against Vibrio alginolyticus, Vibrioparahaemolyticus, Vibrio mimicus, Vibrio campbelli, Vibrio vulnificus, Vibrio harveyi and Photobacterium damselae. Oreochromis mossambicus were fed 5% of their body mass per day for 45 days, and those fed the experimental diets showed a greater increase in mass (111-139%) over the 45 days compared to those that received the control diet (98%). The specific growth rate of O. mossambicus fed the four diets was also significantly greater (1.66-1.93%) than control (1.52%) diet-fed fish. The blood plasma chemistry analysis revealed that protein, albumin, globulin, cholesterol, glucose and triglyceride levels of experimental fish were significantly higher than that of control fish. Packed cell volume of the blood samples of experimental diet-fed fish was also significantly higher (34.16-37.95%) than control fish (33.0%). Leucocrit value, phagocytic index and lysozyme activity were enhanced in fish fed the plant extract-supplemented diets. The acetone extract of the plants inhibited growth of Vibrio spp. and P. damselae with extracts from W. somnifera showing maximum growth inhibition. A challenge test with V. vulnificus showed 100% mortality in O. mossambicus fed the control diet by day 15, whereas the fish fed the experimental diets registered only 63-80% mortality at the end of challenge experiment (30 days). The cumulative mortality index for the control group was 12,000, which was equated to 1.0% mortality, and accordingly, the lowest mortality of 0.35% was registered in H(4)-diet-fed group.