The hypothesis of this work was that chronic treatment with carvedilol (CAR) administered in a nanomicelles-based formulation (CAR-NMs), which increases CAR oral bioavailability, is more effective than a conventional liquid CAR formulation (CAR-LCF) and is comparable to chronic treatment with losartan (LOS) in improving hemodynamic parameters and preventing target organ damage (TOD) in spontaneously hypertensive (SH) rats. Chronic treatment with CAR-NMs significantly improved central hemodynamic parameters (systolic and diastolic blood pressure (BP) and its variability) to a similar extent as LOS, and with superior efficacy than CAR-LCF. Although LOS was more effective than CAR-NMs and CAR-LCF in reducing peripheral systolic BP, both LOS and CAR-NMs, in contrast to CAR-LCF, were able to significantly reduce short-term BP variability indexes. Both CAR formulations and LOS significantly reduced aortic media wall thickness and interstitial collagen deposition, and lowered TNF-α expression in left ventricle (LV) in SH rats. Only CAR-NMs significantly reduced IL-6 expression and were more effective in reducing ventricular TGF-β expression in LV of SH rats. These findings suggest that encapsulation of CAR in NMs improved its ability to control central hemodynamics in SH rats when compared with CAR-LCF, mainly due to a greater effect on carotid systolic BP and short-term BP variability, resulting in a higher protection against TOD compared to CAR-LCF.