With accelerated urbanization, air pollution has become an environmental problem that requires urgent resolution. Intensified inflammation, atopic dermatitis, and itchy skin have been reported in humans exposed to increasing PM2.5 concentrations. PM2.5 is the particulate matter whose aerodynamic equivalent diameter is less than or equal to 2.5 μm in ambient air. Madecassoside, a pentacyclic triterpenoid active component, which is found in and extracted from the plant Centella Asiatica, possesses unique pharmacological properties, such as anti-inflammatory activity, which are used to treat skin wounds. This study investigated the effects of madecassoside in terms of pyroptosis antagonism, cell membrane repair promotion, and skin barrier repair using THP-1 and HaCaT cells stimulated with PM2.5. We measured IL-1β and LDH contents in culture supernatants of THP-1 cells. The expressions of the proteins related to cell membrane repair and skin barrier repair were detected by western blotting, quantitative reverse transcription PCR and immunofluorescence. We found that madecassoside reduced the release of the inflammatory factor IL-1β and the lytic cell death marker lactate dehydrogenase and repaired PM2.5-induced gasdermin D-mediated cell membrane damage. Further, madecassoside may have the potential to promote skin barrier repair by alleviating skin barrier-related protein damage and nuclear transfer. Therefore, madecassoside possesses anti-PM2.5 stimulating activity through repairing gasdermin D-mediated cell membrane damage and possibly protecting the skin barrier, indicating that madecassoside has good anti-inflammatory repair efficacy.