Silymarin, a flavonoid compound derived from the milk thistle plant (Silybum marianum) is well-known for its hepatoprotective, antioxidant, immunomodulatory, and anti-inflammatory properties. Therefore, this study sought to evaluate the effect of silymarin and micelle silymarin (MS) supplementation on Pacific white shrimp (Litopenaeus vannamei). The experimental diets were formulated to include MS at levels of 0.25, 0.5, 1.0, 2.0, and 4.0 g/kg or silymarin at levels of 1.0 and 2.0 g/kg in the basal diet (Con, M0.25, M0.5, M1, M2, M4, S1 and S2, respectively). Juvenile shrimp (0.98 g) were fed with experimental diets (four replicates) for 42 days. The growth metrics were significantly (P < 0.05) increased in M0.25, M0.5, and M1 groups compared to the Con group. Feed conversion ratio decreased (P < 0.05) in M0.5, M1, and M2 groups, whereas the protein efficiency ratio increased (P < 0.05) in M0.5 and M1 groups compared to the Con group. Phenoloxidase, lysozyme, glutathione peroxidase, and superoxide dismutase activities were enhanced (P < 0.05), with the highest levels observed in the M0.5 group. Malondialdehyde level decreased (P < 0.05) in M1 and M2 groups compared to the Con group. Total protein increased (P < 0.05) in M0.25, M0.5 and S1 groups compared to the Con group. AST levels were significantly reduced (P < 0.05) in shrimp fed M0.5, M1, M2, M4, and S2 groups, and ALT levels decreased (P < 0.05) in M1 and S2 groups compared to Con group. Wall thickness was significantly higher (P < 0.05) in the M0.5 group, and villi length increased (P < 0.05) in M0.25, M0.5, and S1 groups. The resistance against Vibrio parahaemolyticus increased; however, no significant differences in cumulative survival were observed (P ˃ 0.05). Significantly higher (P < 0.05) proPO levels were observed in M0.5, M1, M2, M4, and S2 groups, whereas higher (P < 0.05) TLR-3 levels were observed in M1 and M2 groups compared to the Con group. TNF-α expression decreased (P < 0.05) in all other dietary treatments compared to the Con group. The findings suggest that dietary silymarin and MS can enhance growth, immune response, antioxidant capacity, gut morphology, and immune gene expression, while reducing lipid peroxidation and inflammation in Pacific white shrimp. The shrimp performance shows no significant difference between silymarin and MS groups at 1% and 2% levels. The optimal suggested inclusion level of MS in shrimp feed is 0.5–1.0 g/kg.