This experiment aimed to investigate the effects of dietary palm kernel meal and enzymatic hydrolysis of palm kernel meal as potential substitutes for traditional ingredients on the physicochemical properties of feed, alongside the growth performance, antioxidant response, and digestive ability in a feeding trial involving largemouth bass. The control diet, labeled as SBM, was formulated to contain approximately 46 % crude protein and 13 % crude lipids. Experimental diets substituted 5 % soybean meal and 3 % wheat flour with 5 % palm kernel meal or enzymatic hydrolysis of palm kernel meal, and 3 % cotton protein concentrate (CPC) labeled as PKM and EPKM. In comparison to the other two experimental groups, the water solubility (WS), pellet durability index (PDI), and floatability showed no significant differences in SBM. The diets PKM and EPKM showed higher bulk density (BD) and hydration time (HT) compared to SBM. The three types of feed used for largemouth bass had no significant effect on their growth performance, body composition, or digestion. However, feeding with EPKM significantly increased the levels of T-AOC, SOD, and GSH-Px in the plasma of largemouth bass, enhancing their antioxidant capacity. Additionally, EPKM reduced the levels of pro-inflammatory factors TNF-α and IL-1β in both the plasma and intestines of largemouth bass, indicating an anti-inflammatory effect. A histological examination of intestinal sections showed that feeding with EPKM increased intestinal wall thickness and villus width, promoting intestinal health. In conclusion, the application of enzymatic hydrolysis of palm kernel meal in the feed of largemouth bass has a positive effect on their health.