Sewage in WWTPs is one of main way to spread antibiotic resistant microbes (ARMs), and beach bay water is in direct contact with human skin. It is necessary to pay attention to remove the ARMs in WWTP sewage and bay water. Our results showed that ARMs and total microbes (TMs) can be effectively removed by S₂O₈^2-/Fe²⁺ in the effluent stage of WWTPs and bay water. Quenching experiments using tert-butyl alcohol, dimethyl sulfoxide and Al₂O₃ as scavengers confirmed that the primary reactive oxidants responsible for microbes removal during the Fe(II)-activated persulfate oxidation process might be SO₄^.- and Fe(IV), rather than ^.OH. The bacterial community shifted and the alpha diversity significantly reduced after treatment. In WWTP group, relative abundance of Firmicutes increased to 8.56%, and potential pathogens such as genus Vibrio decreased to 0.03% in bay water after treatment. The ecological toxicity to the environment of S₂O₈^2-/Fe²⁺ further illustrated that the mortality of indicator species Oryzias latipes did not increase after treatment, and the dosage of 60/30 μM can be potentially ideal dosage of S₂O₈^2-/Fe²⁺. This study revealed Fe(II)-activated persulfate oxidation as an eco-friendly and economical method could reduce TMs and ARMs in WWTP sewage and bay water.