Display omitted •Zn2In2S5 shell effectively inhibits oxidation of oxygen vacancies on MoO3-x.•Zn2In2S5 can effectively regulate oxygen defect concentration of MoO3-x.•MoO3-x/Zn2In2S5 heterojunction exhibits superior CIP removal and ABR inactivation.•The correlation between pollutant active sites and degradation path was revealed. Water pollution caused by organic pollutants and water-borne pathogens has posed a serious threat to human health. Herein, a fully encapsulated core–shell MoO3-x@Zn2In2S5 S-scheme heterojunction was constructed for efficient removal of ciprofloxacin (CIP) and disinfection of antibiotic-resistant bacteria (TC-E. coli). The excellent catalytic performance is attributed to the synergistic advantages of optimized oxygen defect concentration, the protection of oxygen vacancy and enhanced photogenerated carrier separation efficiency. The MO@ZIS-15 with optimum defect density can remove 92.6 % of CIP in 120 min and inactivate 7.7 log TC-E. coli in 75 min. Furthermore, the developed MO@ZIS-15 system has excellent anti-anion and organic matter interference ability, and also exhibit good utilization potentiality in practical water. Combining theoretical calculations and liquid chromatography-mass spectrometry (LC-MS), the structure–function correlation between different CIP active sites and degradation pathway are revealed. Toxicity prediction and cytotoxicity experiments demonstrated that photocatalytic treatment can effectively reduce the ecotoxicity of degradation products. This work provideds a novel vision to design high-efficiency plasma-based photocatalysts for the removal of organic contaminants and disinfection of antibiotic-resistant bacteria.