Cyanobacteria are photosynthetic microorganisms occurring in different environments, including freshwater and marine ecosystems. Cyanobacterial blooms, boosted by climate change, is a global issue with significant ecological and economic impacts on both water quality (recreational and drinking water) and functioning of aquatic ecosystems. Cyanobacteria indeed produce an array of cyanometabolites including potent toxins (cyanotoxins), such as microcystins among others. To guarantee the safety of surface water intended for drinking in water supply systems, public water suppliers use different water treatment steps including disinfection to remove harmful contaminants (including cyanobacteria). In Italy, the pre-oxidation of raw surface water is conducted using chlorine-based agents whose efficacy and safety in removing both cyanobacterial cells and cyanotoxins is still debated. An inter-disciplinary study was conducted on Microcystis aeruginosa cultures treated with different chlorine-based pre-oxidants (different agents at different doses and exposure times). Liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) revealed that microcystins dominated the toxin profile and that all the treatments induced cell damage with a decrease of toxin contents in biomass versus an increase of toxins released in water whereas some differences were observed among treatments. Untargeted LC-HRMS screening also revealed the presence of a new cyanopeptoline-type peptide whose tentative structure was hypothesized based on its fragmentation pattern.