: Although considerable success has been shown for antihypertensive medications, the resistant hypertension and hypertension-related organ damages are still the important clinical issues and pose as high health and economic pressure. Therefore, novel therapeutic techniques and antihypertensive drugs are needed to advance more effective therapy of hypertension and hypertension-related disease to ameliorate mortality and healthcare costs worldwide. In this review, we highlight the latest progress in supporting the therapeutic potential of Elabela (ELA), a recently discovered early endogenous ligand for G-protein-coupled receptor apelin peptide jejunum, apelin receptor. Systemic administration of ELA exerts vasodilatory, antihypertensive, cardioprotective, and renoprotective effects, whereas central application of ELA increases blood pressure and causes cardiovascular remodeling primarily secondary to the hypertension. In addition, ELA drives extravillous trophoblast differentiation and prevents the pathogenesis of preeclampsia (a gestational hypertensive syndrome) by promoting placental angiogenesis. These findings strongly suggest peripheral ELA's therapeutic potential in preventing and treating hypertension and hypertension-related diseases including cardiovascular disease, kidney disease, and preeclampsia. Since therapeutic use of ELA is mainly limited by its short half-life and parenteral administration, it may be a clinical application candidate for the therapy of hypertension and its complications when fused with a large inert chemicals (e.g. polyethylene glycol, termed polyethylene glycol-ELA-21) or other proteins (e.g. the Fc fragment of IgG and albumin, termed Fc-ELA-21 or albumin-ELA-21), and new delivery methods are encouraged to develop to improve the efficacy of ELA fragments on apelin peptide jejunum or alternative unknown receptors.