This study aimed to investigate the modulatory effects of soybean-derived peptides IVPQ and IAVPT, which were initially identified as potent ACE2-activating peptides, on Ang II-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) and the underlying mechanisms via ACE2 activation. IVPQ and IAVPT ameliorated Ang II-induced malignant migration and NO reduction in HUVECs via the activation of the ACE2/Ang-(1-7)/MasR axis, resulting in Ang II degradation and decreased Ang II signaling. These protective effects were attenuated by ACE2 knockdown to different degrees, which was possibly due to different mechanisms of activating ACE2, where IAVPT directly activated ACE2 at a concentration of 1.0 × 10