The on-site sustainable electrochemical synthesis of hydrogen peroxide (H2O2) in natural seawater holds significant practical value in the fields of energy storage and environmental treatment. However, the poisoning of the active sites by ions such as Cl−, Ca2+, and Mg2+ in natural seawater significantly inhibits the ORR activity of the catalyst. Herein, the 2e− ORR performance of S, N co-doped carbon materials in natural seawater was investigated, focusing on the anti-Ca2+/Mg2+ poisoning mechanism of S-doped carbon structures. The data indicate a Faradaic efficiency of 94.2 % for H2O2 production, with a yield of 3.52 mol/(gcat h), and an approximate 100 % sterilization of bacteria and inactivation of chlorella within 10 min. S-doped carbon structures demonstrated enhanced H2O adsorption and dissociation properties during the ORR process, optimized the micro-environment of the catalytic interface, effectively inhibited Ca2+ and Mg2+ deposition. Moreover, S-doping altered the N coordination structure, further enhancing the 2e− ORR selectivity of the catalyst. This study demonstrates the high selectivity of 2e− ORR in natural seawater, offering guidance for designing catalysts using in the complex environment and advancing marine energy storage and environmental treatment technologies.