The effects of different doses of Solanum nigrum extract enriched diets, on the immune response and disease resistance of tiger shrimp, Penaeus monodon against Vibrio harveyi, were examined. Total hemocyte count (THC) and hyaline cell (HC) of P. monodon fed with 0.1% and 1.0% doses of S. nigrum extract enriched diets significantly increased to the control against V. harveyi whereas semi-granular cell (SGC) and granular cell (GC) at 0.1% dose diet. Phenoloxidase activity, superoxide dismutase activity, glutathione peroxidase activity, and glutathione peroxidase activity significantly enhanced of P. monodon fed with 0.1% and 1.0% doses of S. nigrum extract enriched diets against V. harveyi. However, the respiratory burst activity significantly enhanced of shrimp fed with 0.1% and 1.0% doses on weeks 2 and 4. The phagocytic activity significantly enhanced all the supplementation doses from weeks 1 to 4 compared to control against pathogen. The cumulative percentage mortality was low in 0.1% and 1.0% doses diets with 35% and 30% whereas high in 0.01% dose diet as 50% compared to control (90%) against pathogen. Therefore, diet containing S. nigrum extract with 0.1% and 1.0% doses were found to enhance the immunity and disease resistance of P. monodon against V. harveyi.