Pterostilbene (PST), a naturally occurring stilbenoid and polyphenol, demonstrates significant antioxidant, antimicrobial, and anti-inflammatory properties. Therefore, this study investigates the effects of dietary PST supplementation on growth, hemolymph physiology, molecular docking analysis, redox status, immune ability, and resistance to Vibrio parahaemolyticus in whiteleg shrimp. For this study, 320 healthy juvenile whiteleg shrimp (4.58 ± 0.36 g) were randomly allocated into four experimental groups. The control group (PST0) received a basal diet. The remaining three treated groups were fed diets supplemented with 100 (PST1), 200 (PST2), or 400 (PST400) mg PST per kg of diet over a 3-month period. The inclusion of PST in shrimp diets significantly improved growth attributes, demonstrating a quartic effect compared to untreated shrimp (p < 0.001). The FCR values in the PST2 and PST4 groups were superior compared to the PST0 (linear effect, p < 0.05). A linear effect was also observed in the survival rate (SR), responding proportionally to the increasing inclusion of PST in the shrimp diets. Supplementing PST significantly increased blood proteins (linear effect, p < 0.05), while liver enzymes (GGT, AST, LDH, and ALT) and lipid profile were quadratically decreased (p < 0.05). PST administration improved quadratically digestive enzymes (amylase, lipase, and protease) in shrimp (p < 0.001) compared to the PST0 diet. The inclusion of PST in shrimp diets resulted in a significant quadratic enhancement of SOD, GSH, and CAT activities compared to the PST-free diet (p < 0.001). PST supplementation in shrimp diets induced a quadratically significant reduction in MDA, IL-4, and IFN-γ compared to the PST0 group (p < 0.001). The study indicates that dietary PST supplementation improved resistance to V. parahaemolyticus, with the PST4 group exhibiting the lowest mortality rate (30%) compared to the control group (60%). Molecular docking analysis indicates a robust binding affinity between the PST and apoptotic markers (caspase-3), and inflammatory (NFκB and TRAF6 receptors) with − 7.57, − 4.73, and − 3.14 kcal/mol. Overall, the inclusion of PST in shrimp diets proved beneficial effects by improving growth, boosting antioxidant activity, and decreasing inflammatory and apoptotic markers. This demonstrates a promising approach for enhancing the overall health and productivity of the shrimp industry.