Cardiovascular diseases (CVDs) are considered the most common disorder and the leading cause of mortality globally. The etiology of CVDs depends on a variety of genetic and acquired parameters. Nowadays, a dramatic surge appeared in published reports to find the association between microRNAs (miRNAs) and CVDs in order to understand the cause of the disease, rapid diagnosis with the introduction of valid biomarkers, and target as a therapeutic approach. Apigenin is a novel nutraceutical flavonoid that cardioprotective properties are suggested. The current review aimed to evaluate the beneficial features of this phytochemical against CVDs with an emphasis on its ability to regulate the miRNAs. The findings demonstrated that Apigenin could regulate cardiac miRNAs, including miR-103, miR-122-5p, miR-15b, miR-155, and miR-33. Consequently, preventing CVDs is possible through different effects such as the promotion of cholesterol efflux, prevention of hyperlipidemia, alteration in ATP Binding Cassette Subfamily A Member 1 (ABCA1) levels, reducing of cardiocytes apoptosis, and retarding myocytes fibrosis. Also, it can regulate signaling pathways, protect against endothelial dysfunction, maintain oxidative balance, and decrease inflammatory factors and reactive oxygen species. Hence, apigenin regulatory characteristics affecting miRNAs expression could introduce this flavonoid as a novel cardioprotective phytochemical against different CVDs.