The skin is routinely exposed to stresses from environmental pollution. These repeated and regular exposures can profoundly affect skin physiology, and may lead to irreversible consequences. We studied the potential of a Schisandra chinensis (S.C.) extract, particularly enriched in lignans, to enhance skin defense mechanisms involved in pollution stress response, with the main pathways involved in skin being Nuclear Factor Kappa B (NF-kB), DJ-1, the nuclear factor erythroid 2-related factor 2 (Nrf2) and aryl hydrocarbon receptor (AhR) signaling pathways. Using an in vitro model, we showed that co-treatment with Urban dust and S.C. extract was able to stimulate the expression of Nrf2 and DJ-1, as well as the decrease of NF-kB and AhR, suggesting that this active extract may provide wide protection for skin against daily environmental insults. In a skin equivalent model stressed by Urban dust, the extract provided a global protection of skin components as shown by key proteins involved in the epidermal barrier. Even if further investigations are needed, we speculate that S.C. extract can be used to buffer the harmful effects of free radicals and enhance the skin barrier,due to air pollutant interactions with the skin, allowing a global preservation of cutaneous structures.