Antibiotics regulate various physiological functions in cyanobacteria and may interfere with the control of cyanobacterial blooms during the application of algaecides. In this study, Microcystis aeruginosa was exposed to H2O2 and glyphosate for 7 d in the presence of coexisting mixed antibiotics (amoxicillin, spiramycin, tetracycline, ciprofloxacin, and sulfamethoxazole) at an environmentally relevant concentration of 100 ng · L−1. The mixed antibiotics significantly (P < 0.05) alleviated the growth inhibition effect of 15–45 μM H2O2 and 40–60 mg · L−1 glyphosate. According to the increased contents of chlorophyll a and protein, decreased content of malondialdehyde, and decreased activities of superoxide dismutase and glutathione S‐transferase, antibiotics may reduce the toxicity of the two algaecides through the stimulation of photosynthesis and the reduction in oxidative stress. The presence of coexisting antibiotics stimulated the production and release of microcystins in the M. aeruginosa exposed to low concentrations of algaecides and posed an increased threat to aquatic environments. To eliminate the secondary pollution caused by microcystins, high algaecide doses that are ≥45 μM for H2O2 and ≥60 mg · L−1 for glyphosate are recommended. This study provides insights into the ecological hazards of antibiotic contaminants and the best management practices for cyanobacterial removal under combined antibiotic pollution conditions.