Glycyrrhiza glabra L. is a species widely spread all over the world, with a long tradition of use in folk medicine. Here, raw and hydrolyzed extracts obtained from roots collected in different geographical areas belonging to the Mediterranean basin were standardized as regards the amount of three main compounds: glycyrrhizin, the most abundant triterpene saponin of licorice, the 18β-glycyrrhetinic acid and the chalcone isoliquiritigenin. Raw and hydrolyzed extracts, as well as their pure single compounds, were investigated for their potential anti-inflammatory properties. The hydrolyzed extracts significantly reduced the production of pro-inflammatory cytokines such as TNF-α, IL-6, NO mediator in LPS-stimulated RAW 264.7 cells. Moreover, they were able to inhibit JAK2 and STAT3 phosphorylated proteins more than pure single standards tested at the same final concentrations, displaying a strength synergism of action. These findings suggest that G. glabra extracts and, more specifically, the hydrolyzed ones could represent interesting sources of potential anti-inflammatory agents able to inhibit the JAK/STAT signaling pathway.