As part of an ongoing search for new anti-inflammatory agents from medicinal plants, five new dimeric and trimeric flavonoids (1–5) were isolated from the roots of Pistacia weinmannifolia. The structures of pistachalcone A (1), pistachalcone B (2), pistaflavanone A (3), pistachalcone C (4), and pistachalcone D (5) were elucidated by the analysis of spectroscopic data. The known compounds rhuschalcone II (6), rhuschalcone VI (7), and pauferrol B (8) were also isolated and identified. Our in vitro analysis found that compounds isolated from P. weinmannifolia root extract exert anti-inflammatory effects in phorbol myristate acetate (PMA)-induced NCI-H292 airway epithelial cells by the suppression of expression levels such as interleukin-8 (IL-8) and mucin 5AC (MUC5AC), which are closely related to the pulmonary inflammatory response in the pathogenesis of COPD. Therefore, these dihydrochalcone derivatives may have value as new starting materials for the development of drug candidates against COPD.