Particulate matters (PM), the main contributor to air pollution, have become a serious issue that threatens human’s health. Skin is the largest organ in humans, as well as the primary organ exposed to PM. Overexposure of PM induces skin damage. Diphlorethohydroxycarmalol (DPHC), an algal polyphenol with the potential of skin protection, has been isolated from the edible brown seaweed Ishige okamurae. The purpose of the present study is to investigate the protective effect of DPHC against PM (ERM-CZ100)-induced skin damage in human dermal fibroblasts (HDF) cells. The results indicated that DPHC significantly and dose-dependently reduced intracellular reactive oxygen species generation in HDF cells. In addition, DPHC significantly induced collagen synthesis and inhibited collagenase activity in ERM-CZ100-stimulated HDF cells. Further study demonstrated that DPHC remarkably reduced the expression of human matrix metalloproteinases through regulation of nuclear factor kappa B, activator protein 1, and mitogen-activated protein kinases signaling pathways in ERM-CZ100-stimulated HDF cells. This study suggested that DPHC is a potential candidate to protect skins against PM-induced damage, and it could be used as an ingredient in pharmaceutical and cosmeceutical industries.