Short-chain fatty acids (SCFAs), metabolites of intestinal microorganisms, have been linked to the occurrence and development of a variety of disorders, including cardiovascular disease (CVD), which is frequently accompanied by a sustaining inflammatory response and aberrant angiogenesis. Accumulating evidence from the study emphasizes that SCFAs are closely connected with the activation of the NLRP3 inflammasome (NACHT, LRR, and PYD domains-containing protein 3) and the process of angiogenesis. This review summarizes emerging literature on the impact of SCFAs on various physiological processes, with a subtle attention on the interaction between SCFAs and CVD (especially atherosclerosis, myocardial infarction, and hypertension), SCFAs and NLRP3 inflammasome, as well as SCFAs and angiogenesis. As a result, we speculate that it is convincing that SCFAs play a mediating role in the microbiota-inflammasome-angiogenesis-CVD axis, opening up a new horizon to investigate the function or level of SCFAs as a therapeutic strategy for CVD.