Gynura bicolor (Roxb. & Willd.) DC., a perennial plant belonging to the Asteraceae family, is originated from the tropical area of Asia. The total hemocyte count (THC), phenoloxidase (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) activity, and lysozyme activity were examined after white shrimp Litopenaeus vannamei had been fed diets containing the water extract of G. bicolor at 0 (control), 0.5, 1.0, and 2.0 g (kg diet)−1 for 7–28 days. The results indicated that these parameters increased accordingly with the amount of extract and time. THCs of the shrimp fed the G. bicolor diets at 1.0 and 2.0 g (kg diet)−1 were significantly higher than that fed the control diet for 14–28 days. For the shrimp fed the G. bicolor diets at 0.5, 1.0, and 2.0 g (kg diet)−1, the PO, RBs, and lysozyme activities reached the highest levels after 7 days, whereas SOD activity reached the highest levels after 14 days. In a separate experiment, white shrimp L. vannamei fed the diets containing the G. bicolor extract for 28 days were challenged with Vibrio alginolyticus at 3 × 106 cfu shrimp−1 and white spot syndrome virus (WSSV) at 1 × 103 copies shrimp−1. The survival rate of the shrimp fed the G. bicolor diets was significantly higher than that of the shrimp fed the control diet at 48–144 h post challenge V. alginolyticus and WSSV. For the shrimp fed the G. bicolor diets at 0.5, 1 and 2 g (kg diet)−1 under challenges of V. alginolyticus and WSSV, their LPS- and β-1,3-glucan-binding protein (LGBP) and peroxinectin (PE) mRNA expressions were significantly higher than those of the challenged control shrimp at 12–96 and 24–144 h post-challenge, respectively. We concluded that dietary administration of a G. bicolor extract could enhance the innate immunity within 28 days as evidenced by the increases in immune parameters (PO, RBs, and lysozyme) and antioxidant enzyme (SOD) activities of shrimp to against V. alginolyticus and WSSV infections.