This study investigates the effect of emodin enriched diet on growth, hematology, and immune response in walking catfish, Clarias batrachus against Aeromonas hydrophila. The basal (control) diet supplemented with emodin at 0.0, 0.1, 0.2, or 0.4 g kg−1 was fed to the experimental groups for a period of four weeks. Feeding infected fish with 0.2 g kg−1 and 0.4 g kg−1 emodin enriched diets resulted in an overall weight gain, enhanced PER and FCR when compared to other diets. The survival rates were 98.3% and 96.7% in 0.1 g kg−1 and 0.4 g kg−1 emodin diet fed groups. Feeding with 0.2 g kg−1 diet the RBC level significantly elevated on week 1 and with 0.4 g kg−1 diet on weeks 2 and 4. The WBC, the percentage of globulin and neutrophils increased significantly with 0.2 g kg−1 diet only on week 4; however with 0.4 g kg−1 diet the increase was observed from week 1–4. The phagocytic activity increased significantly on being fed with 0.4 g kg−1 diet on week 2 while with 0.2 g kg−1 and 0.4 g kg−1 diets the increase manifested only on week 4; the respiratory burst activity also significantly increased on week 4 whereas increased the complement activity on weeks 2 and 4. The superoxide dismutase (SOD) activity was high on being fed with 0.4 g kg−1 diet on week 1; with 0.2 g kg−1 or 0.4 g kg−1 diets the increase was observed on weeks 2 and 4. The serum IgM level significantly increased when fed with 0.4 g kg−1 diet whereas the lysozyme activity was enhanced with 0.2 g kg−1 and 0.4 g kg−1 emodin diets on weeks 2 and 4. The percentage cumulative mortality was 10% with 0.1 g kg−1 or 0.2 g kg−1 diets while with 0.2 g kg−1 diet it was 15%. The results demonstrate that as a feed additive emodin acts as an immunostimulant enhancing the specific and nonspecific immune defense affording increased disease protection, enhances better growth and boosts hematology parameters in C. batrachus against A. hydrophila infection.