Methylnissolin-3-O-β-d-glucopyranoside (MNG) and methylnissolin (MN) are pterocarpan derivatives that are found in plants, such as Astragalus membranaceus. There are limited existing studies on the potential health benefits of MNG, and currently there is no evidence to suggest that MNG has any impact on skin-aging. Tumor necrosis factor-alpha (TNF-α) plays a significant role in skin aging by promoting chronic inflammation, damaging skin cells, and impairing the skin's natural repair mechanisms. Targeting TNF-α or its downstream signaling pathways may be a promising strategy for preventing or reversing skin-aging. We tested the effect of MNG and MN on skin-aging by inducing cell inflammation and oxidative stress with TNF-α in HDFs. MNG and MN significantly reduced the TNF-α-induced secretion of matrix metalloproteinase-1 (MMP-1). However, MNG has more beneficial compound for oral administration than MN in pharmacokinetics analysis. The mechanism underlying the anti-skin-aging effect of MNG is related to the suppression of TNF-α-induced reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPKs) phosphorylation. Our results suggest that MNG is a potential candidate for preventing skin-aging induced by TNF-α.