Antibiotic resistance genes (ARGs) have become as emerging contaminant with great concerns worldwide due to their threats to human health. It is thus urgent to develop techniques to degrade ARGs in water. In this study, MoS@FeO (MF) particles were fabricated and used to activate peroxymonosulfate (PMS) for the degradation of four types of free DNA bases (T, A, C, and G, major components of ARGs) and ARGs. We found that MF/PMS system could effectively degrade all four DNA bases (T within 10 min, A within 30 min, C within 5 min, and G within 5 min) in very short time. During the reaction process, MF could activate PMS to form the reactive radicals such as ·OH, SO, O, and O, contributing to the degradation of DNA bases. Due to the low adsorption energy, high charge transfer, and great capability for PMS cleavage, MF exhibited excellent PMS adsorption and activation performances. MoS in MF could enhance the cycle of Fe(III)/Fe(II), improving the catalytic performance. Excellent catalytic performances of MF/PMS system were achieved in complex water matrix (including different solution pH, coexisting of anions and natural organic matter) as well as in real water samples (including tap water, river water, sea water, and sewage) especially under high salinity conditions due to the generation of Cl radicals and HClO species. MF/PMS system could also efficiently degrade ARGs (chromosomal kan and plasmid gmrA) and DNA extracted from antibiotic resistant bacteria (ARB) in super-short time. Moreover, complete disinfection of two types of model ARB (E. coli K-12 MG 1655 and E. coli S17-1) could also be achieved in MF/PMS system. The high degradation performances of MF/PMS system achieved in the reused experiments and the 14-day continuous flow reactor experiments indicated the stability of MF particles. Due to the magnetic property, it would be convenient to separate MF particles from water after use via using magnet, facilitating their reuse of MF and avoiding potential water contamination by catalysts. Overall, this study not only provided a deep insight on Fe/Mo-triggered PMS activation process, but also provided an effective and reliable approach for the treatment of DNA bases, ARGs, DNA, and ARB in water.