The antibacterial effect of the drugs against Vibrio alginolyticus in vitro and the drugs on the resistance to diseases of Epinephelus coioides were studied. This study aimed to screen traditional Chinese medicines formulas and Chinese and western medicines formulas which can prevent V. alginolyticus diseases of E. coioides. We had the bacteriostatic test on traditional Chinese medicines formulas against V. alginolyticus in vitro. The ratios of Terminalia chebula, Radix paeoniae and Glycyrrhiza uralensis of Chinese medicines formulas Ⅰ, Ⅱ, Ⅲ were 0.9:1.3:0.9, 1.2:0.9:1.0, and 1:1:1, respectively. The groups with 3 replicates per treatment of feed containing the drugs feed additives at 2.2% respectively, were fed to E. coioides. The ratio of T. chebula, R. paeoniae and G. uralensis were different in Chinese medicines formulas trial groupⅠ, Ⅱ, Ⅲ. The ratios of T. chebula, R. paeoniae, G. uralensis and enrofloxaci were different in Chinese and western medicines formulas trial groupⅣ, Ⅴ. Results revealed that the concentration of Chinese medicines formulas Ⅲ (200 mg/mL) was the best formula. The mortality for 40 d in test groups were as follows:control groupⅡ > control group Ⅳ > control group Ⅲ > trial group Ⅲ > trial groupⅡ > trial groupⅠ > trial group Ⅴ > trial group Ⅵ > trial group Ⅳ > control groupⅠ. The ratio of T. chebula, R. paeoniae and G. uralensis of Chinese medicines formulaⅠwas 0.9:1.3:0.9. The ratios of T. chebula, R. paeoniae, G. uralensis and enrofloxaci in Chinese and western medicines formula Ⅳ were different. These are the best formulas. The Chinese and western medicines formula is better than the Chinese medicines formula. Results showed that by adding the formulas, the capacity of disease resistance can be improved.