The relationship between grape seed-derived procyanidin extract components and their bioactivity was explored. The monomeric and dimeric structures only acted as anti-inflammatory agents. Similarly, pure C1 trimer was highly effective on LPS-activated macrophages. To reproduce all of the bioactivities of the total extract, a fraction enriched with trimeric structures was needed. This trimeric-enriched fraction was divided into subfractions, the most bioactive of which contained two compounds with a molecular weight equal to a trimer (865) and a dimer-gallate (729), according to spectrometric analysis. Thus, it may be concluded that a mixture of both molecules reproduces the bioactivity in glucose metabolism (3T3-L1), lipid metabolism (HepG2) and macrophage functionality (RAW 264.6).