A series of O-aryl- and alkyl-substituted phosphorodithioates were designed and synthesized as hydrogen sulfide (H₂S) donors. H₂S releasing capability of these compounds was evaluated using fluorescence methods. O-aryl substituted donors showed slow and sustained H₂S release while O-alkylated compounds showed very weak H₂S releasing capability. We also evaluated donors' protective effects against hydrogen peroxide (H₂O₂)-induced oxidative damage in myocytes and donors' toxicity toward B16BL6 mouse melanoma cells.