The antibiotic resistance of bacteria in aquaculture is a concern for many scientists around the world. Both aquatic animals and humans were able to infect Vibrio parahaemolyticus, leading to economic losses for the aquaculture sector worldwide. Therefore, the goal of this research is to evaluate the antibiotic resistance of V. parahaemolyticus, the causative agent of acute hepatopancreatic necrosis disease (AHPND), in white-leg shrimp (Litopenaeus vannamei) intensively farmed in Ben Tre and Soc Trang provinces of the Mekong Delta, Vietnam. The antibiotic susceptibility of 32 strains of V. parahaemolyticus to 12 antibiotics was determined by the disk diffusion method. The findings revealed that V. parahaemolyticus isolates are highly sensitive to flumequine (94%), florfenicol (88%), ceftazidime (82%), rifampicin (76%), ciprofloxacin (74%), tetracycline (74%), and doxycycline (68%). Meanwhile, these isolates are highly resistant to amoxicillin (88%), colistin (72%), and cephalexin (66%). In addition, most bacterial strains in the study showed multidrug resistance (resistant to at least 3 antibiotics), of which V. parahaemolyticus bacterial strains resistant to 3 antibiotics account for the highest percentage (34%), followed by 4 antibiotics (19%), resistance to 5 antibiotics accounted for 16%, and the lowest rate was resistance to 7 antibiotics (3%).