Diclofenac sodium was extensively used for treating arthritis, osteoarthritis and skeletal muscular injuries, which ultimately caused troubles for aquatic organisms as well as human beings. In this study, homogeneous catalytic advanced oxidation processes, including Fe²⁺/persulfate, Fe²⁺/peroxymonosulfate and Fe²⁺/H₂O₂, were used for the degradation of diclofenac sodium in water, without using UV-C light. About 89, 82 and 54% DCF sodium was decomposed by Fe²⁺/persulfate, Fe²⁺/peroxymonosulfate and Fe²⁺/H₂O₂, respectively, in 60 min. The degradation of diclofenac sodium followed the pseudo first-order kinetics, in all cases. The degradation efficiency of diclofenac sodium was significantly affected in the presence of various anions, such as NO₃⁻, HCO₃⁻ and SO₄²⁻. The mineralization studies revealed 62, 45 and 32% total carbon removal by Fe²⁺/persulfate, Fe²⁺/peroxymonosulfate and Fe²⁺/H₂O₂, respectively, in 60 min. In addition, the degradation byproducts of diclofenac sodium were determined by FTIR analysis. The results revealed that the Fe²⁺/oxidant system, particularly Fe²⁺/persulfate, was a promising technology for the elimination of toxic pharmaceuticals, such as diclofenac sodium, from the water environment.