The quantity of mineral processing wastewater (MPW) is large and contains residual thiol collectors, which easily cause environmental pollution. Herein, we systematically investigated the catalytic performances and underlying mechanisms of iron sulfide minerals (pyrite, marcasite, and pyrrhotite) for the activation of peroxymonosulfate (PMS) to treat MPW containing various thiol collectors (ethyl xanthate (EX), butyl xanthate (BX), diethyldithiocarbamate (DDTC)). Density functional theory (DFT) calculation results indicated that electron-rich Fe atoms in pyrite and marcasite acted as electron donors for PMS adsorption and cleavage, while pyrrhotite with electron-deficient Fe atoms has no PMS adsorption site. In particular, pyrite has stronger reactivity in comparison with marcasite due to more electron transfer and the lower thermodynamic and kinetic energy barrier of the reaction. Meanwhile, the efficient electron transfer of pyrite with strong F−S covalent bonds facilitated the regeneration of Fe(II), thus improving the catalytic performance. As a result, pyrite exhibited the highest total organic carbon (TOC) removal efficiency for real MPW, which was 1.12-fold and 1.63-fold of that on marcasite and pyrrhotite, respectively. This study highlights the structure−activity relationship of iron sulfide minerals and provides new insights into the PMS activation mechanism of sulfur-containing catalysts for MPW treatment.