Metalloproteinases (MMPs) are zinc-dependent endopeptidases responsible for the hydrolysis of various component of extracellular matrix such as gelatin and collagen. MMPs, namely MMP-2 and MMP-9 correlate with cardiovascular events in patients. We sought to determine whether supplementation with polyphenol-rich Cynara cardunculus (wild artichoke, traditional component of the Mediterranean diet) modulates MMP-9 expression and activity in cell cultures. A fully characterized C. cardunculus extract was able to inhibit, in a dose-dependent manner, the gelatinolytic activity of secreted MMP-9 and both secretion and human MMP-9 promoter-driven transcription. Analysis by HPLC of the Cynara extract identified polyphenols such as luteolin, apigenin, and caffeic acid, among others. However, testing a mix of the individual components suggested that the inhibitory effects of C. cardunculus are due to minor constituent fraction(s) as a whole. In promoting the health benefits of the Mediterranean diet, the role of wild plants as important meal components deserves further reappraisal.