Clamworm is a biological bait with high nutritional value, widely used in promoting gonadal maturation of shrimp brood stock. However, as most clamworm occur in wild environments, they are prone to carrying pathogenic bacteria and viruses, posing a potential disease risk for farmed shrimp. To eliminate the pathogens carried by clamworm, antibiotics are often used by immersion. Due to the disadvantages of using antibiotics, novel safe and effective alternative products must be developed urgently. Sorbic acid, malic acid, citric acid, and other organic acids and their salts are commonly used as preservatives and fungicides in food and have potential development value for biological sterilization of aquatic bait. To research the profile of Vibrio pathogens carried by bait clamworm and establish effective pathogen elimination technology, the pathogen species and Vibrio load in 10 coastal areas of China were investigated. Sodium citric acid, povidone iodine, potassium sorbate, sodium dehydroacetate, malic acid, potassium dimethyl acid, propionic acid, and a Vibrio-killing product (VKP)—a commercial product containing citric acid and acid calcium sulfate—were employed to test the bactericidal effect in vitro in this study. The lowest and safest bactericidal concentrations of citric acid, povidone iodine, and VKP were tested in vitro for the elimination effect of Vibrios in clamworm. Additionally, protein, fat, cholesterol, and vitamin E content changes in clamworm after soaking in citric acid, povidone iodine, and VKP for 3 h were analyzed. The results displayed that the sample clamworm carried Vibrio alginolyticus, V. harveyi, V. owensii, V. parahaemolyticus, and V. parahaemolyticus with detection rates of 86.7%, 20.0%, 13.3%, 13.3%, and 6.7%, respectively. The highest and lowest pathogenic Vibrio loads in the sample were 7.0×10⁴ and 2.0×10³ cfu/g, respectively. The minimum bactericidal concentrations of the nine drugs in vitro from low to high were povidone-iodine (10.0×10^–3 g/L), formic acid (0.5 g/L), VKP (1.0 g/L), citric acid/malic acid/propionic acid (1.2 g/L), potassium dicarboxylate (1.6 g/L), sodium dehydroacetate (12.0 g/L), and potassium sorbate (30.0 g/L). The inactivation rates of Vibrio in vivo were 96.2%, 66.4%, 99.9% and 97.7%, 98.0% 100.0%, respectively, when the clamworm were soaked in the citric acid, povidone-iodine and VKP solutions at the minimum effective bactericidal concentration for 0.5 and 3 h. Safe concentrations of the three drugs were 48.9, 120.3 and 963.0 mg/L, respectively, meanwhile the contents of protein, fat, cholesterol, and vitamin E in the clamworm were significantly reduced compared with those in the control group (P＜0.05) after the 3 h treatment. The results suggest that the clamworm has a great biosafety risk as biological bait, and the soaking treatment in organic acids can reduce the pathogenic bacterial load. The results of this study provide a basis for the comprehensive prevention and control of shrimp diseases.