The electrosynthesis of hydrogen peroxide (H2O2) via a selective two-electron oxygen reduction reaction (2e- ORR) presents a green and low-energy-consumption alternative to the traditional, energy-intensive anthraquinone process. This review encapsulates the principles of designing relational electrocatalysts for 2e- ORR and explores remaining setups for large-scale H2O2 production. Initially, the review delineates the fundamental reaction mechanisms of H2O2 production via 2e- ORR and assesses performance. Subsequently, it methodically explores the pivotal influence of microstructures, heteroatom doping, and metal hybridization along with setup configurations in achieving a high-performance catalyst and efficient reactor for H2O2 production. Thereafter, the review introduces a forward-looking methodology that leverages the synergistic integration of catalysts and reactors, aiming to harmonize the complementary characteristics of both components. Finally, it outlines the extant challenges and the promising avenues for the efficient electrochemical production of H2O2, setting the stage for future research endeavors.