Sulfide-modified zero-valent iron (S-Fe0) is regarded as a promising method to enhance the catalytic activity of Fe0 for peroxymonosulfate (PMS) activation. However, the roles of sulfidation and the application of the sulfidation treatment method are worth to further investigation. In our study, the effects of the S/Fe ratio, Fe0 dosage, and initial pH on sulfadiazine (SDZ) removal were investigated. The characterization of S-Fe0 with SEM, XPS, contact angle and Tafel analysis confirmed that the formation of sulfur species on the Fe0 surface could enhance the catalytic performance of Fe0. S2− played the major role and SO32- played the minor role in accelerating the conversion of Fe3+ to Fe2+. EPR tests, radical quenching and quantitative determination experiments identified •OH as playing the major role and SO4•− also playing an important role in SDZ removal in S-Fe0/PMS system. Sulfidation produced no notable change in the role of •OH and SO4•−. A possible degradation pathway of SDZ was proposed. Effect of sulfidation on various sizes of Fe0 was also studied which demonstrated that the smaller sizes of Fe0 (< 8 µm) were more effective in the sulfidation method treatment. S-Fe0/PMS system also showed a good performance in removing antibiotics in natural fresh water.