Atmospheric pressure plasma jet (APPJ) gained great interest due to its effectiveness as selective non-lethal technique with low operational costs. In this study, argon APPJ system was designed and the generated cold plasma was applied in disinfection of microbial cells.Argon APPJ was generated by blowing argon through capillary metallic tube inserted in alumina and powered by 8-25 kHz sinusoidal voltage waveform. The plasma applied in inactivation of microbes by direct exposure of cell suspension, approximately 10 mm below jet nozzle, for different intervals. Interference of organics in exposure medium, on lethal activity of plasma was investigated.APPJ jet induced high levels of reactive oxygen (ROS) and nitrogen species (RNS). Jet length increased with applied voltage and flow rate in laminar mode, but decreased with flow rate in turbulent mode. Percent reduction in living cell count was 98.3 and 94.1%, for E. coli and S. aureus suspended in water after 30s of exposure, respectively, with 2.7- and 2-folds increase in plasma lethal activity, as compared with LB broth medium. D-values (Decimal Reduction Time) were increased from 34-333, 37-476 and 139-385 s for E. coli, S. aureus and C. albicans in water and complex liquid organic media, respectively.Designed argon APPJ system can be used in disinfection of different microbes. Plasma antimicrobial activity drastically decreased in presence of organic matter. The generated plasma can be promising approach for treatment of diseases, especially caused by antibiotic-resistant pathogens.