Electro-Fenton (EF) is an emerging technology with well-known outstanding oxidation power; yet, its application to the treatment of inorganic contaminants has been largely disregarded. Thiosalts are contaminants of emerging concern in mine water, responsible for delayed acidity in natural waterways. In this study, EF was used to treat thiosalts in synthetic and real mine water. Thiosulfate (S2O32-) solutions were first used to optimize the main parameters affecting the process, namely, the current density (2.08-6.25 mA cm-2), temperature (4 vs 20 °C), and S2O32- concentration (0.25-2 g L-1). S2O32- was almost completely removed in 2 h of treatment at 6.25 mA cm-2, while temperature played no important role in the process efficiency. The optimal conditions were then applied to treat a real sample of contaminated mine water, resulting in complete S2O32- and S4O62- oxidation to SO42- in 90 min at 6.25 mA cm-2 (95% removal in only 60 min). The reaction mechanisms were investigated in detail based on the quantification of the main degradation byproducts. This study opens new possibilities for EF application to the treatment of thiosalt-contaminated mine water and other oxidizable inorganic-impacted wastewaters.