Despite the known anti-inflammatory, antibacterial, and antioxidant properties of bee venom (apitoxin), its application for promoting growth and health in shrimp (Litopenaeus vannamei), remains largely unexplored. This study explored the effects of bee venom (BV) encapsulated nano-chitosan (BV-CSNPs) on the health and disease resistance of white shrimp. Two hundred forty shrimp (mean weight 6.0 ± 0.02 g) were randomly assigned to four groups (n = 60 per group), each consisting of four replicate hapa (1 m³ each) stocked with 20 shrimp. Shrimp were fed either a basal diet (control) or diets added with 0.1, 0.2, or 0.3 mg of bee venom encapsulated nano-chitosan (BV-CSNPs) per kg of feed for 63 days. Following the feeding trial, shrimp (n = 30 form each group) were challenged with Vibrio parahaemolyticus, and survival rates were subsequently assessed. Supplementation with BV-CSNPs in shrimp diets resulted in significantly enhanced weight gain and feed efficiency compared to the basal diet (P < 0.05). BV-CSNPs supplementation significantly increased hemocyte counts and phenoloxidase levels in a dose-dependent manner (P < 0.05). The highest dose (0.3 mg/kg) also significantly enhanced lysozyme and phagocytic activities compared to the other treatments (P < 0.05). Significant increases in the activities of antioxidant enzymes (SOD and CAT) and digestive enzymes (lipase, amylase and protease) were observed in all BV-CSNP-supplemented groups compared to the control group (P < 0.05). Regarding gene expression, a dose-dependent increase in the expression of immune genes associated with the proPO system (LGBP, PX, and ppA) and antioxidant genes (cytMnSOD and mtMnSOD) was observed in shrimp fed diets supplemented with BV-CSNP (0.1, 0.2, and 0.3 mg/kg). Histopathological analysis revealed normal hepatopancreas and intestinal tissue structure, with increased hepatopancreatic B-cell secretion and improved intestinal histomorphology in BV-CSNP-treated shrimp. These groups also exhibited lower mortality rates after the challenge with V. parahaemolyticus. Dietary inclusion of BV-CSNP proved highly effective in promoting shrimp growth and overall health. The benefits observed include enhanced digestive enzyme activity, improved intestinal integrity, robust antioxidant and innate immune responses, and effective protection against V. parahaemolyticus infection.