Calycotome villosa subsp. intermediais used in traditional medicine for the prevention and self-treatment of a variety of illnesses, including diabetes mellitus, obesity, and hypertension. The present study aims to investigate thein vivo,ex vivo, andin vitrohypoglycemic and hypotensive effects of the lyophilized aqueous extract ofCalycotome villosa subsp.intermediaseeds (CV) onMeriones shawisubmitted to hypercaloric diet and physical inactivity (HCD/PI) for 12 weeks. This diet induces a type 2 diabetes/metabolic syndrome phenotype with hypertension. Furthermore, HCD/PI decreased aorta contraction due to noradrenaline, enhanced L-arginine, and depressed insulin-evoked relaxation, while the relaxing effects of the NO donor SNAP and of diazoxide were unchanged.In vivoexperiments showed that the oral administration of the CV extract (50 mg/kg b.wt) for 3 consecutive weeks significantly attenuated the development of type 2 diabetes, obesity, dyslipidemia, and hypertension. These effects may involve the improvement of lipid metabolism, insulin sensitivity, systolic arterial pressure, and urine output. Additionally,ex vivoandin vitroinvestigations revealed that CV treatment improved vascular contraction to noradrenaline, induced a slight aorta relaxation in response to carbachol, increased the vasorelaxation effect evoked by insulin, and depressed the L-arginine evoked relaxation. However, CV did not change the endothelium-independent vasorelaxation response evoked by SNAP or diazoxide. Hence, the present study provides useful information and supports the traditional use of CV in the prevention and self-treatment of numerous ailments. Overall, it can be concluded thatCalycotome villosa subsp.intermediaseed extracts might be useful in the management of type 2 diabetes and hypertension.