The recognition of hydrogen sulfide (H₂S) has been evolved from a toxic gas to a physiological mediator, exhibiting properties similar to NO and CO. On the one hand, H₂S is produced from L-cysteine by enzymes of cystathionineγ-lyase (CSE) and cystathionineβ-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST) in combination with aspartate aminotransferase (AAT) (also called as cysteine aminotransferase, CAT); on the other hand, H₂S is produced from D-cysteine by enzymes of D-amino acid oxidase (DAO). Besides sulfide salt, several sulfide-releasing compounds have been synthesized, including organosulfur compounds, Lawesson’s reagent and analogs, and plant-derived natural products. Based on garlic extractions, we synthesized S-propargyl-L-cysteine (SPRC) and its analogs to contribute our endeavors on drug development of sulfide-containing compounds. A multitude of evidences has presented H₂S is widely involved in the roles of physiological and pathological process, including hypertension, atherosclerosis, angiogenesis, and myocardial infarcts. This review summarizes current sulfide compounds, available H₂S measurements, and potential molecular mechanisms involved in cardioprotections to help researchers develop further applications and therapeutically drugs.