The　transmission　of　antibiotic　resistance　genes　(ARGs)　and　the　propagation　of　antibiotic　resistant　bacteria　(ARB)　threaten　public　health　security　and　human　health,　and　greener　and　more　efficient　disinfection　technologies　are　expected　to　be　discovered　for　wastewater　treatment.　In　this　study,　natural　pyrite　and　ascorbic　acid　(AA)　were　proposed　as　environmental-friendly　activator　and　reductant　for　periodate　(PI)　activation　to　inactivate　ARB.　The　disinfection　treatment　of　PI/pyrite/AA　system　could　inactivate　5.62　log　ARB　within　30　min,　and　the　lower　pH　and　higher　PI　and　natural　pyrite　dosage　could　further　boost　the　disinfection　efficiency.　The　1　O　2　and　SO　4　center　dot-　were　demonstrated　to　be　crucial　for　the　inactivation　of　ARB　in　PI/pyrite/AA　system.　The　disinfection　process　destroyed　the　morphological　structure　of　ARB,　inducing　oxidative　stress　and　stimulating　the　antioxidant　system.　The　PI/pyrite/AA　system　effectively　reduced　the　intracellular　and　extracellular　DNA　concentration　and　ARGs　abundance,　inhibiting　the　propagation　of　ARGs.　The　presence　of　AA　facilitated　the　activation　of　PI　with　natural　pyrite　and　significantly　increased　the　concentration　of　Fe2+　2　+　in　solution.　The　reusability　of　natural　pyrite,　the　safety　of　the　disinfection　by-products　and　the　inhibition　of　ARB　regeneration　indicated　the　application　potential　of　PI/pyrite/AA　system　in　wastewater　disinfection.