Blackberry (Rubus ulmifolius Schott) and mugwort (Artemisia campestris L.) are plants traditionally used to treat various pathologies, including hypertension. The vasodilatory and hypotensive effects of blackberry were investigated through experiments in rat models (n = 5 rats per group) and compared with those of mugwort, which had been demonstrated previously. A nutrigenomic experiment in mouse models (n = 3 mice per group) was also performed for both plants to associate biomarker genes with these effects. Additionally, a phytochemical analysis was carried out to identify the bioactive molecules responsible for the cardiovascular effects. A dose-dependent hypotensive effect and a carbachol-like vasodilatory effect were observed for blackberry and compared with those of mugwort. These effects were associated with the deregulation of gene expression related to vessel lumen expansion (Amotl2, Cdh1 and Tfcp2l1) and circulatory system morphology and activity (Dsp, Ahnak, Prcp and Smtnl2) for both plants. Their functional potential also includes antiproliferative, antimicrobial, anti-inflammatory and appetite-regulating properties. Chlorogenic acids, quercetin and kaempferol derivatives were identified in blackberry as the main bioactive molecules likely to be responsible for its cardiovascular effect. The blackberry extract exhibited a vasorelaxant effect 20 times greater than mugwort, attributed to the exclusive presence of the hypotensive galloyl-bis-HHDP glucose derivative and a more pronounced upregulation of Tfcp2l1, which is involved in epithelial cell maturation. This study validates the traditional use of blackberry and mugwort in treatment of hypertension, identifies marker genes and bioactive molecules for vasodilatory and hypotensive effects and expands their potential applications to cancer prevention, inflammation reduction and appetite regulation.