•We propose a new way to treat Microcystic aeruginosa in water via plasma oxidation.•Our approach can inactivate algal cells and degrade microcystins simultaneously.•The mechanism is mainly due to the attack of ROS on the cells and the toxins.•Poly-synchronous tools, e.g., EEM and FCM were employed to analyze the processes. We proposed a method to inactivate M. aeruginosa by using discharge plasma taking at the gas-solution interface supplied by DC power. Multiple analysis techniques including fluorescence excitation–emission matrix (EEM) and flow cytometry (FCM) were used to reveal the inactivation mechanism of M. aeruginosa. The photosynthetic pigment contents including phycocyanin, chlorophyll and metabolites were examined quantitatively. The DC glow discharge plasma caused an increased level of reactive oxygen species (ROS), and the damage of M. aeruginosa cells are mainly attributed to the oxidative stress including OH attack and H2O2 oxidation. Our findings demonstrate that plasma oxidation is a promising technology for inactivation of M. aeruginosa cells with simultaneous removal of microcystins and so it may lead us to a new route to efficient treatment of cyanobacterial blooms.