The remarkable performance of SO4•— based advanced oxidation processes in improving waste activated sludge (WAS) dewatering has recently received considerable attention. However, its potential effect on the removal of emerging pollutants is often overlooked. In this study, two types of pretreatment methods (S2O82-/Fe2+ and SO32-/Fe2+) were employed to comprehensively evaluate their performance in improving the dewatering of WAS and the removal of antibiotic resistance genes (ARGs) and pathogenic microorganisms. At the optimal dosage of 1.2/1.5 mmol-S2O82-/Fe2+/g-VS, the capillary suction time reduction rate of WAS after S2O82-/Fe2+ was 1.8 times than that of SO32-/Fe2+. Notably, both S2O82-/Fe2+ and SO32-/Fe2+ could remove the 12 types of ARGs identified in WAS. Nonetheless, S2O82-/Fe2+ was more effective in removing ARGs, with a range of removal rate (0.96–2.17 log-units), and reduced the propagation and proliferation potential of residual ARGs. Furthermore, the coliforms content in WAS after S2O82-/Fe2+ decreased significantly with a minimum of 1.84 ± 0.24 log (MPN/g-TS) compared to SO32-/Fe2+. Further analysis indicated that the redistribution of bound extracellular polymeric substances (EPS) in WAS, especially the variations in protein, was the key factor affecting the dewaterability. In contrast to SO32-/Fe2+, the S2O82-/Fe2+ could quickly destroy the EPS structure to release bound water, accelerate the dissociation of WAS flocs, and cause cell lysis and DNA dissolution because of the continuous production and accumulation of SO4•— in the hostile conditions inside. Therefore, S2O82-/Fe2+ is an efficient, economical, and green method to improve WAS dewatering and the removal of pollutants.