Pulmonary injury is defined as a progressive inflammation. Extensive pro-inflammatory cytokines are secreted from alveolus, associated with the production of reactive oxygen species (ROS) and apoptosis. The model of endotoxin lipopolysaccharide (LPS)-stimulated lung cells has been applied to mimic the pulmonary injury. Some antioxidants and anti-inflammatory compounds can be used as chemopreventive agents of pulmonary injury. Quercetin-3-glucuronide (Q3G) has been showed to exert antioxidant, anti-inflammatory, anti-cancer, anti-aging and anti-hypertension effects. The aim of the study is to examine the inhibitory potential of Q3G on pulmonary injury and inflammation in vitro and in vivo. Firstly, human lung fibroblasts MRC-5 cells pre-treated with LPS were demonstrated to cause survival loss and ROS generation, were recovered by Q3G. Q3G also exhibited the anti-inflammatory effects on the LPS-treated cells with a reduction in the activation of NLRP3 [nucleotide-binding and oligomerization domain (NOD)-like receptor protein 3] inflammasome, leading to pyroptosis. Also, Q3G showed the anti-apoptotic effect in the cells might be mediated via inhibition of mitochondrial apoptosis pathway. To further explore in vivo pulmonary-protective effect of Q3G, C57BL/6 mice were intranasally exposed to a combination of LPS and elastase (LPS/E) to perform the pulmonary injury model. The results revealed that Q3G ameliorated pulmonary function parameters and lung edema in the LPS/E-induced mice. Q3G also suppressed the LPS/E-stimulated inflammation, pyroptosis and apoptosis in the lungs. Taken together, this study suggested the lung-protective potential of Q3G via downregulation of inflammation, pyroptotic and apoptotic cell death, contributing to its chemopreventive activity of pulmonary injury.