Increasing contamination of groundwater by heavy metals could potentially hamper the basic sanitation based on septic system in developing countries. Therefore, this paper evaluated wastewater treatment by electrochemical activation of hydrogen peroxide (EAHP), persulfate (EAP), and free chlorine (EAFC) to simultaneously eliminate aqueous organic matter and heavy metals. Sacrificial iron anodes under galvanostatic regime activated the batch-injected oxidants under uncontrolled pH, to avoid extra cost of control in decentralized processes (e.g., household use) to treat domestic wastewater. Response surface methodology (RSM) was used to determine the optimized conditions for EAP ([persulfate]0 = 25 mM, 24.4 mA/cm2), EAFC ([free chlorine]0 = 35.5 mM, 44.4 mA/cm2), and EAHP ([H2O2]0 = 91.1 mM, 45 mA/cm2) towards total organic carbon (TOC) removal. Treatment of real wastewater under optimum conditions significantly reduced chemical oxygen demand (COD) and TOC in all treatments, complying with lenient effluent standards as well as the added benefit of complete As(V) and Cr(VI) removal. Although EAP and EAFC provided superior removal of TOC (70−75%) and COD (73–100%) within 3 h, respectively, effluent toxicity and operation cost (76–85 USD/m3) were relatively high. EAHP was the best available option to secure non-toxic effluent with the least cost (63 USD/m3).​