Due to the public and environmental health impact of cyanotoxins, investigations have been focused on finding environmental friendly algaecides from aquatic plants. The present study had the objective to evaluate the population control and physiological response of Microcystis aeruginosa (Kützing) Kützing (strain BCCUSP232) exposed to Pistia stratiotes L. extracts. Aqueous and ethanolic extracts of P. stratiotes at different concentrations (10, 25, and 50 mg L⁻¹) were submitted to M. aeruginosa and reduced significantly (p<0.05) the cyanobacterium cell density. The ethanolic extract presented the greatest growth inhibition of the strain at the highest concentration. During exposure to P. stratiotes extracts, intracellular hydrogen peroxide levels, malondialdehyde content, and antioxidant enzymes (peroxidase, catalase, and glutathione S-transferase) activities increased in M. aeruginosa, while total protein concentration decreased when compared to the control group. Superoxide dismutase (SOD) activities presented a sharp decline, suggesting superoxide radical and peroxide accumulation. This implied that SOD was a target for bioactive substance(s) from aqueous and ethanolic extracts of P. stratiotes. Phytochemical screening of the extracts revealed that the ethanolic extract presented 93.36 mg gallic acid equivalent (GAE) per gram dry weight (g⁻¹ DW) total polyphenols and 217.33 mg rutin equivalent (RE) per gram dry weight total flavonoids, and for the aqueous extract, 5.19 mg GAE g⁻¹ DW total polyphenols and 11.02 mg RE g⁻¹ DW total flavonoids were detected. Gas chromatography (GC)/mass spectrometry (MS) analyses of the ethanolic and aqueous extracts presented palmitic acid ethyl ester as major allelochemical. In view of these results, it can be concluded that P. stratiotes showed potential in controlling M. aeruginosa populations.