Allelochemicals have been proven to be effective in inhibiting microalgae. However, there is limited knowledge regarding their effect on cyanobacteria in the case of repeated exposure, which is more environmentally relevant. In the present study, the effects of multiple low-dosage additions and single high-dosage addition of Myriophyllum spicatum extracts toward Microcystis aeruginosa were compared based on cell density, photosynthetic response, antioxidative response, and microcystins (MCs) production. Although the cumulative exposure content of M. spicatum extracts was the same (5 g/L), our results showed that algal growth was promoted in repeated low-dosage exposure, whereas single high-dosage exposure inhibited cell growth and decreased photosynthetic activity with the highest inhibition rate of cell density reaching 58.2 %. Oxidative stress occurred in all treatments exposed to M. spicatum extracts, as indicated by the increased catalase (CAT) activity and superoxide Dismutase (SOD) activity. It is noteworthy that oxidative damage to the cell membrane only occurred in single high-dosage exposure as indicated by the malondialdehyde (MDA) contents, which were 1.9, 2.1, 2.8, and 2.7 times higher than that of the control group from day 2 to day 5, respectively. Moreover, repeated low-dosage exposure could promote MC synthesis as indicated by the up-regulated mcyD gene abundance. Cell lysis may be responsible for the increased MCs release in single high-dosage exposure treatment since active transport of MCs was suppressed as indicated by mcyH gene abundance. This study revealed differential responses of M. aeruginosa to single and repeated exposure to allelochemicals, shedding light on the allopathy control of cyanobacteria.