Antioxidative catalytic activities of trans-3,4-dihydroxyselenolane (DHS^red), a water-soluble cyclic selenide, were investigated in the reaction of hydrogen peroxide with three different thiol substrates, monothiol glutathione (GSH), dithiol dithiothreitol (DTT^red), and polythiol reduced ribonuclease A (RNase A) having eight thiol groups along the polypeptide chain For all the thiol substrates, DHS^red exhibited higher glutathione peroxidase (GPx)-like antioxidative catalytic activities than the corresponding linear selenide, that is, Se(CH₂CH₂OH)₂ The rate-determining step of the catalytic cycle was unambiguously assigned to the oxidation process of the selenide rather than the reduction process of the selenoxide intermediate The enhanced catalytic activities of DHS^red can be ascribed to the cyclic structure, which elevates the HOMO energy level and makes the selenium atom more exposed to the surroundings.