Microcystis aeruginosa is one of the dominant algae in the “phytoplankton bloom” phenomenon. A high density of microcystins (MCs) are produced when algae have explosive growth, which can damage the water environment and pose a great threat to aquatic animals, plants, and human health. Duckweed (Landoltia punctata) is a morphologically highly degraded flowering plant with a short growth cycle and wide environmental adaptability. Importantly, duckweed can grow in eutrophic water and has great potential in water remediation. The present study aims to analyze the physiological and biochemical changes of L. punctata when co-culturing with M. aeruginosa in the laboratory. Our results showed that all the biomass, chlorophyll content, antioxidant enzyme activities, and amylase activity of L. punctata increased in 2 × 108 cells/L and 4 × 108 cells/L for M. aeruginosa, and also significantly reduced in 1.6 × 109 cells/L for M. aeruginosa, while cytotoxic substance (malondialdehyde (MDA)) content showed a completely opposite trend. After co-culturing, it was found that the MC content in L. punctata reduced to 138.87 g/g, and the MC removal rate was 29.48%. These results indicate that L. punctata can grow normally in high-density M. aeruginosa, which paves the way for L. punctata’s bioremediation of water polluted by M. aeruginosa.