Objective: Argyreia speciosa is a popular Indian medicinal plant. It has long been used in the traditional Ayurvedic Indian medicine for various diseases. The present work was designed to evaluate anti-inflammatory potential of hydroalcoholic extract of A. speciosa roots using mouse model of HCl-induced acute lung injury (ALI) by conducting a dose–response studies. Materials and Methods: The extract was given once orally at a dose of 50, 100, or 200 mg/kg b.wt. 90 min before HCl administration. Lung tissue of different group of mice was analyzed for the recruitment of inflammatory cells, redox status, and mRNA expression of pro-inflammatory genes to evaluate the anti-inflammatory effects of the extract. Results: Our results showed that the extract reduced HCl-induced lung inflammation in a dose-dependent manner. The neutrophil numbers in bronchoalveolar lavage fluid (BALF) were almost completely abrogated at a dose of 100 mg/kg b.wt. The severe reduction in neutrophils was accompanied with reduced pulmonary edema as the total protein content in BALF was found to be decreased substantially. In addition, the extract prevented the HCl-mediated oxidative stress in lungs as reflected by the normalization of levels of reactive oxygen species, malondialdehyde, redox status, and catalase activity. Extract seems to blunt the activity of redox-sensitive transcription factor nuclear factor-kappa B (NF-κB) as it suppressed the gene expression of ALI-linked pro-inflammatory cytokines, namely, interleukin-1 β and tumor necrosis factor-alpha. Conclusion: Overall, our data provide evidence that cocktail of natural phytochemicals present in hydroalcoholic extract of A. speciosa protects against HCl-induced ALI in mice potentially by curbing oxidative stress and consequent activation of NF-κB in the tissue.