: The existence of Vibrio cholera (V. cholera) is a major health problem in many parts of the world; therefore, the treatments of V. cholera have always remained necessary for public safety, health, and environmental protection. In the last few decades, plasma discharges have proven to be a novel technique of sterilization against infectious bacteria such as V. cholera. In this research, a low-pressure plasma (LPP) technique has been introduced for the degradation of multidrug resistant V. cholera. The V. cholera strains with 107 CFUs (colony-forming units) were treated by low-pressure plasma, with and without H2O2 injection into the sterilization chamber, to investigate and report the adverse effects of plasma on V. cholera. The results demonstrated that plasma treatment has significant effects on the degradation of V. cholera in the presence of H2O2 vapors inside the plasma sterilization chamber. The time-course study of the bactericidal effects revealed that there is no regeneration or increase in the number of V. cholera colonies after plasma treatment.