Members of the genus Pulicaria have been used in traditional medicine for alleviating several complaints as they have a rich pool of biometabolites. Acute lung injury (ALI) is a serious disease with an elevated mortality rate. The present investigation aimed to evaluate the total phenolic and flavonoid contents and antioxidant capacity of the methanolic extract of P. petiolaris Jaub. and Spach. (PP) (Asteraceae). Moreover, the potential protective potential of PP against lipopolysaccharide-(LPS)-induced ALI was assessed. PP is a rich source of phenolics and flavonoids. The total phenolic content (TPC) was 68.05 mg gallic acid equivalent (GAE)/g dried extract, and the total flavonoid content (TFC) was 45.86 mg quercetin equivalent (QE)/g dried extract. Additionally, PP possessed a promising DPPH-scavenging activity, with an IC 50 =27 μg/mL. Our results showed that PP lessened LPS-induced lung injury. PP effectively reduced pulmonary edema as it lowered total protein and the lung wet/dry weight (W/D) ratio in the bronchoalveolar lavage fluid (BALF). It also significantly ameliorated the level of lactate dehydrogenase (LDH) in the BALF and improved the histopathological lesions in the lung tissue. LPS-induced inflammatory cell infiltration was greatly depressed in PP-treated animals. PP showed antioxidant capacity as it reduced the LPS-induced increase in the lipid peroxidation marker, malondialdehyde (MDA). It also increased the activity of superoxide dismutase (SOD) and the content of reduced glutathione (GSH). This study indicates that PP significantly decreased LPS-induced inflammation in the LPS-mediated ALI murine model, suggesting that it may become a significant preventive strategy for treating nonspecific inflammation of the lungs.