Large volumes of oil sands process-affected water (OSPW) are produced during the extraction of bitumen from oil sands in Alberta, Canada. The degradation of a model naphthenic acid, cyclohexanoic acid (CHA), and real naphthenic acids (NAs) from OSPW were investigated in the presence of peroxydisulfate (S2O82–) and zerovalent iron (ZVI). For the model compound CHA (50 mg/L), in the presence of ZVI and 500 mg/L S2O82–, the concentration decreased by 45% after 6 days of treatment at 20 °C, whereas at 40, 60, and 80 °C the concentration decreased by 20, 45 and 90%, respectively, after 2 h of treatment. The formation of chloro-CHA was observed during ZVI/S2O82– treatment of CHA in the presence of chloride. For OSPW NAs, in the presence of ZVI alone, a 50% removal of NAs was observed after 6 days of exposure at 20 °C. The addition of 100 mg/L S2O82– to the solution increased the removal of OSPW NAs from 50 to 90%. In absence of ZVI, a complete NAs removal from OSPW was observed in presence of 2000 mg/L S2O82– at 80 °C. The addition of ZVI increased the efficiency of NAs oxidation by S2O82– near room temperature. Thus, ZVI/S2O82– process was found to be a viable option for accelerating the degradation of NAs present in OSPW.