Insufficient biodegradability of antibiotics (e.g., oxytetracycline, OTC) and the accompanying antibiotic resistance gene (ARG) spreading risk have been a serious concern in wastewater treatment plants. This study developed a microbial-driven persulfate activating-cycling system (MPCS) relying on the iron-reducing capacity of Shewanella oneidensis to sustainably degrade OTC and prevent ARG elevation. In MPCS, a nanosized bio-magnet shell (20-60 nm) was bio-generated and incorporated with S. oneidensis to activate peroxydisulfate and produce free radicals to attack OTC, removed by 98.78 % in 120 min. S. oneidensis metabolism re-generated the bio-magnet and cleared the toxic intermediates. Despite the stress of OTC and free radicals, S. oneidensis sustained (live/death ratio of 74.50 %: 25.50 %) under bio-magnet shell protection, showing a strong energy metabolism and iron-reducing strength. The tight coupling of biodegradation and advanced oxidation process (AOP) greatly improved degrading efficiency (132.65 %-2369.44 % higher than single biodegradation or AOP). MPCS continuously operated 5 cycles efficiently, exhibiting a diverse degrading pathway with less toxic intermediates than the single treatment. Notably, MPCS functioned well without peroxydisulfate, as the S. oneidensis produces low-level hydrogen peroxide as the AOP substrate, achieving favorable OTC elimination. Especially, the expression of sixteen tetracycline-related ARGs dropped by 62.94 %-100 % in MPCS than biodegradation, indicating resistance control advantage under bio-magnet shell protection and the synergism effect of AOP and biodegradation. This study spontaneously recyclably combined biodegradation and AOP to simultaneously eliminate antibiotics and ARGs, which provided a potential approach to control the drug resistance risk.