Vibrio spp. Were a cause of serious disease in aquaculture. This study aimed to develop a Vibrio spp. inhibition method that is safe and friendly for the environment, namely bacteriophage (phage). Vibrio spp. and their phages were isolated from shrimp, water, and mud from farms in Mekong Delta provinces (Kien Giang, Soc Trang, and Bac Lieu provinces). Then, the phage influence on the bacterial concentration and the toxR gene was investigated by comparing the gene sequences pre- and post-infection. The polymerase chain reaction identified 31 strains of Vibrio spp., including 9 of Vibrio parahaemolyticus. Then, using several isolated Vibrio spp. as hosts, 32 phage strains were isolated. Results found that each bacteriophage affected the Vibrio toxR gene in specific ways. Phage ST9 and phage ST10 did not change bacterial concentration, but they could change nucleotides at 4 positions compared to the V. parahaemolyticus sequence. Nevertheless, phage KG6 could reduce bacterial concentration but did not affect gene sequences. The bacteriophages can affect bacteria through several mechanisms, including reducing the bacterial concentration via the lytic process or affecting genes encoding bacterial virulence. These findings open a new direction in phage therapy research if such an effect can reduce or neutralize bacterial virulence.