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To investigate the effects of tributyrin supplementation in soybean oil (SO)-based diet, three equal-protein (50%) and equal-lipid (12%) experimental diets were formulated: the fish oil (FO) diet, the SO diet, and the tributyrin (TB) diet with 0.20% tributyrin supplemented in the SO-based diet. Each diet was randomly fed to triplicate tanks with 20 fish (initial weight, 9.00 ± 0.02 g) per tank (300 L). Fish were fed to apparent satiation twice daily for 56 days. The whole body, muscle, and intestine tissue samples were collected for analysis. The results indicated that tributyrin partly reversed the final body weight (TB [39.92 ± 0.33 g] versus SO [35.12 ± 0.55 g]) and feed efficiency rate (TB [0.99 ± 0.01] versus SO [0.92 ± 0.01]) decrease and the whole body crude lipid content increase, caused by the replacement of dietary FO by SO. A significant increase in the polyunsaturated fatty acid proportion was observed in the muscle tissue of fish fed the tributyrin diet. The improvement of growth performance mediated by tributyrin supplementation may be attributed to the significant improvement of the intestinal morphology, as indicated by the morphology structure section and molecular parameters. Dietary tributyrin may decrease the SO-induced pro-inflammatory response, characterized by significantly decreased expression of a pro-inflammatory gene (IL-6) and significantly increased expression of an anti-inflammatory gene (IL-10) (P < 0.05). In conclusion, dietary 0.20% tributyrin supplementation in the SO-based diet improved growth performance, affected muscle fatty acid composition, and improved intestinal histology structure in the juvenile yellow drum. [ABSTRACT FROM AUTHOR]