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A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available <i>Prodefen^&#174; Plus</i>. MtS was induced by HFD (45%) in male Wistar rats. Half of the MtS animals received <i>Prodefen^&#174; Plus</i> for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. <i>Prodefen^&#174; Plus</i> supplementation did not affect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. <i>Prodefen^&#174; Plus</i> supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with <i>Prodefen^&#174; Plus</i> could be considered an interesting non-pharmacological approach in MtS.