Cyanobacterial proliferation is one of the most harmful hazards, in both freshwater and marine ecosystems. Cyanobacteria are well known for their ability to produce a wide variety of bioactive compounds, some of which have been described as allelochemicals. There is growing evidence that these secondary metabolites play an important role in shaping community composition through biotic interactions; however, for the most part, their biological role and mode of regulation of the production are poorly understood. In temperate eutrophic freshwaters, Microcystis and Planktothrix often co-occur, with Planktothrix being an early colonizer and Microcystis appearing subsequently. By integrating LC-MS/MS molecular networking and an innovative experimental design, we tested if the production of cyanopeptides by co-existing species could be regulated through interspecifc interactions. We investigated chemically mediated interactions between two cyanobacteria, a toxic M. aeruginosa strain and a non-toxic P. agardhii strain, using a combined approach of co-cultures and metabolomic profiling. More precisely, we evaluated changes in growth, morphology and metabolites production and release by both interacting species. Interestingly, culturing Microcystis with Planktothrix resulted in a reduction of the growth of Planktothrix together with a decrease of its filament size and alterations in the morphology of its cells. Ours untargeted metabolomic profiling allow to observe that the production of specific intracellular compounds by Planktothrix was not different between mono and co-culture conditions. Concerning Microcystis, the number of specific intracellular compounds was higher under co-culture condition than under monoculture. In general, Microcystis produced a lower number of intracellular compounds under monoculture than Planktothrix, and a higher number of compounds than Planktothrix under co-culture condition. These results suggest that specific compounds produced by Microcystis in the presence of Planktothrix have been specifically produced as potential allelochemicals. Identification of compounds specifically involved in the observed physiological and morphological changes of Planktothrix cells is still in progress.