BACKGROUND: The dermal extracellular matrix (ECM) is a dynamic scaffold composed mainly of proteins, with collagen as the key structural component providing resilience and support to the skin. Post-menopause, declining estrogen levels lead to a significant reduction in skin health, notably a 30% decrease in collagen types I and III within 5 years. AIM: To discover natural extracts that stimulate collagen production. METHODS: We utilized PathwayStudio to analyze protein-protein interactions and identify regulators of essential collagen types. Our study assessed Glycyrrhiza uralensis extract's ability to boost collagen production and enhance dermal density both in vitro and in vivo. RESULTS: PathwayStudio analysis highlighted phytoestrogens including glycyrrhizin, isoliquiritigenin, liquiritigenin, liquiritin, and glabrol, as potential candidates. Liquorice rhizome (G. uralensis), used in traditional Chinese medicine, is rich in phytoestrogens like liquiritigenin. The G. uralensis extract increased collagen I and III gene expression and pro-collagen I protein levels in human dermal fibroblasts and inhibited UVB and pollution-induced matrix metalloproteinase-1 (MMP1) production. In an in vivo study, a topical formulation containing the extract significantly improved dermal density after 56 days, measured by the DUB SkinScanner. CONCLUSIONS: These findings suggest G. uralensis extract as a promising agent for enhancing collagen production and skin health, particularly in postmenopausal women. Further research is needed to explore its mechanisms and long-term effects.