Photocatalytic H 2 O 2 production offers a sustainable alternative to energy-intensive routes; however, a random heterointerface and poor visible-light response of the photocatalyst restrict its activity. Herein, a distinct organic-inorganic S-scheme heterojunction was rationally designed by coating polydopamine onto In 2 S 3 (denoted as 3PIS), exhibiting a defined interfacial area and extending visible-light absorption, leading to enhanced H 2 O 2 evolution (89.6 μmol g –1 min –1 ; 5-fold higher than pristine In 2 S 3 ) in pure water without sacrificial agents. The 3PIS architecture enables prolonged carrier lifetime, facilitates charge accumulation, and electron delivery to activate molecular oxygen via a two-electron oxygen reduction reaction. The reduced thermodynamic barriers enable the formation of critical *OOH intermediates, which undergo subsequent protonation and reduction to generate H 2 O 2 . In addition, the photogenerated H 2 O 2 achieves 100% bacterial inactivation, further reflecting the stable and selective H 2 O 2 production over 3PIS. This study furnishes a potentially extendable design of organic-inorganic heterojunctions toward sustainable solar-to-chemical energy conversion.