Hydrogen sulfide (H₂S) is an endogenous gasotransmitter that plays important roles in redox signaling. H₂S overproduction has been linked to a variety of disease states and therefore, H₂S-depleting agents, such as scavengers, are needed to understand the significance of H₂S-based therapy. It is known that elevated H₂S can induce oxidative stress with elevated reactive oxygen species (ROS) formation, such as in H₂S acute intoxication. We explored the possibility of developing catalytic scavengers to simultaneously remove H₂S and ROS. Herein, we studied a series of selenium-based molecules as catalytic H₂S/H₂O₂ scavengers. Inspired by the high reactivity of selenoxide compounds towards H₂S, 14 diselenide/monoselenide compounds were tested. Several promising candidates such as S6 were identified. Their activities in buffers, as well as in plasma- and cell lysate-containing solutions were evaluated. We also studied the reaction mechanism of this scavenging process. Finally, the combination of the diselenide catalyst and photosensitizers was used to achieve light-induced H₂S removal. These Se-based scavengers can be useful tools for understanding H₂S/ROS regulations.