Myocardial infarction is one of the leading causes of death worldwide. Thus, protection against myocardial ischemia-reperfusion injury is particularly important to improve the prognosis of myocardial infarction. Recently, hydrogen sulfide (H2S) has been reported to possess a protective effect against myocardial ischemia-reperfusion injury. However, an effective gas delivery system to release H2S controllably at an appropriate concentration needs to be further investigated. In this study, a new H2S-releasing hydrogel system was constructed and applied in an experimental I/R model of rats. The administration of the hydrogel significantly ameliorated microvascular obstruction, prevented myocardial fibrosis, and attenuated cardiac inflammation. This suggested that the novel H2S-releasing hydrogel represented a promising therapeutic strategy targeting myocardial ischemia-reperfusion injury.