Hydrogen peroxide (H2O2) as a strong oxidant, is widely used in various chemical industries and environmental remediation processes. In this study, we developed an innovative method for cost-effective production of H2O2 by using a microbial reverse-electrodialysis electrolysis cell (MREC). In the MREC, electrical potential generated by the exoelectrogens and the salinity-gradient between salt and fresh water were utilized to drive the high-rate H2O2 production. Operational parameters such as air flow rate, pH, cathodic potential, flow rate of salt and fresh water were investigated. The optimal H2O2 production was observed at salt and fresh water flow rate of 0.5 mL min−1, air flow rate of 12–20 mL min−1, cathode potential of −0.485 ± 0.025 V (vs Ag/AgCl). The maximum H2O2 accumulated concentration of 778 ± 11 mg L−1 was obtained at corresponding production rate of 11.5 ± 0.5 mg L−1 h−1. The overall energy input for the synthesis process was 0.45 ± 0.03 kWh kg−1 H2O2. Cathode potential was the key factor for H2O2 production, which was mainly affected by the air flow rate. This work for the first time proved the potential of MREC as an efficient platform technology for simultaneous electrosynthesis of valuable chemicals and utilization of salinity-gradient energy.