Myriophyllum aquaticum has shown potential allelopathic effects for the biocontrol of cyanobacteria and cyanotoxins. However, the composition of allelochemicals and their biological effects may be influenced by seasonal changes. In this study, we investigated the impact of aqueous extracts of M. aquaticum collected in different seasons on the growth of Microcystis aeruginosa and the concentration of microcystin-LR. Plant samples were extracted using ultrasound cycles in aqueous solutions, and extracts at varying concentrations (0.1, 10, and 100 mg/L) and a control treatment were inoculated with M. aeruginosa, and cell growth was analyzed using a Neubauer chamber. Photosynthetic pigment quantification was used to measure physiological effects and liquid chromatography was used to evaluate the microcystin-LR concentrations. The extracts of plants collected during autumn and winter exhibited higher inhibition of M. aeruginosa growth and a reduction in photosynthetic pigments compared to those collected during spring and summer. These results can be explained by the higher presence of phenolic compounds in the composition of extracts from autumn and winter. Microcystin-LR concentrations were decreased at 10 and 100 mg/L, with the highest efficiency observed in autumn, while spring showed lower efficiency. Our findings suggest that M. aquaticum extracts have inhibitory potential on M. aeruginosa, particularly during the autumn season, making them a promising nature-based solution for the biocontrol of harmful algal blooms.