Vibriosis is a common bacterial infection in shrimp that causes mortality in hatcheries and farms. Various steps have been initiated to increase the resistance against bacterial pathogens and decrease the mortality rate through improved culture conditions and feed. Arthrospira platensis (Spirulina), a blue-green alga, is a good source of protein and other nutrients and helps to improve digestion. The effects of the methanol extract of A. platensis on the survival rate and resistance against vibriosis were studied. The minimum inhibitory concentration of the extract for Vibrio species and in vivo antibacterial screening were investigated using Litopenaeus vannamei. Vibrio alginolyticus was inhibited with 2000 µg mL-1 extract and the other two species were inhibited by 1500 µg mL-1 extract. Furthermore, the mortality rate and antioxidant enzyme levels of shrimps injected with pathogens reduced and increased after treatment with the methanol extract, respectively. The survival rate of V. parahaemolyticus and V. harveyi-challenged shrimps were 33.3% and 50%, respectively, after 168 h. The survival rate of V. alginolyticus-infected shrimp reduced (16.6%) 168 h after injection. All surviving shrimp developed resistance to Vibrio pathogens. This study indicated that the bioactive compounds in A. platensis could not only effectively prevent bacterial infection, but also serve as eco-friendly and cost-effective immune stimulants.