This work investigated the inactivation of Microcystis aeruginosa (MA) with contact glow discharge electrolysis (CGDE). The influences of applied voltage, current and treatment time on the inactivation rate were critically examined. Based on the above results, the optimal conditions were chosen to sufficiently utilize chemically active species and enhance the inactivation of MA. Under the optimal conditions (voltage: 530 V; current: 30 mA; treatment time: 20 min), the inactivation rate of algae was more than 90% within 5 days incubation after inoculating. At the same time, the concentrations of Chlorophyll-a and dehydrogenase decreased, which demonstrated that 20 min CGDE treatment could effectively inhibit the growth of MA and caused deterioration of cell integrity. The present work would provide strong evidence to support the utilization of CGDE on the inactivation of MA in aqueous solution.