Cardiovascular disease (CVD) and related pathologies are the leading cause of death worldwide. Fruits and vegetables are known to improve CVD, an effect that has been associated with flavonoid intake. The aim of this study was to simultaneously evaluate the acute effect of a low molecular grape seed proanthocyanidin extract (LM-GSPE) on two of the main risk factors of CVD, high blood pressure (BP) and dyslipidaemia, using high-fat diet-fed rats. Therefore, male Wistar rats that were cafeteria diet fed for 10 weeks were administered with 375 mg/kg of body weight of LM-GSPE, and the BP as well as plasmatic and hepatic parameters were determined at 6 h post-administration. The BP and plasmatic and hepatic lipid were decreased 6 h after the LM-GSPE administration. Moreover, the liver lipid peroxidation products decreased after the LM-GSPE treatment, indicating a reduction in oxidative stress. However, hepatic-reduced glutathione or plasma angiotensin converting enzyme activity was not altered by the LM-GSPE. In conclusion, grape proanthocyanidins is able to simultaneously reduce more than one risk factor for CVD by decreasing the BP and improving hypertriglyceridaemia at least in part due to an improvement in oxidative stress. These results open up the possibility of using grape proanthocyanidins in functional foods for CVD improvement.