Lianhua Qingke (LHQK) has been utilized as a complementary therapy for respiratory diseases like tracheobronchitis and acute exacerbations of COPD in China. However, its therapeutic efficacy and underlying mechanisms for COPD remain elusive. This study aimed to elucidate the mechanisms underlying the effects of LHQK on COPD, focusing on its anti-senescence properties. The therapeutic effects of LHQK were assessed by chronic cigarette smoke exposure induced COPD mice model. Lung function, histopathology investigation, cytokines detection and bio-molecular analysis were conducted to assess the impact of LHQK on pulmonary inflammation, mucin secretion, and cellular senescence of cigarette smoke (CS)-induced COPD mice. A comprehensive analysis identified a total of 41 compounds as the key compounds of LHQK. Oral administration of LHQK markedly reversed the decline in pulmonary function, suppressed inflammation and mucus secretion, mitigated emphysema, and histopathology damage in lungs of COPD mice. In addition, LHQK attenuated secretory phenotype associated with cellular senescence in pulmonary and circulatory, and reduced the senescence-associated markers levels, such as SA-β-gal, miR-125a-5p, p21, p27 and p53. Network pharmacology and molecular assays indicated that LHQK enhanced Sp1 and SIRT1 expression, resulting to repression of HIF-1α, finally alleviating cellular senescence in COPD mice. LHQK demonstrates potential as a complementary therapy for COPD, attenuating CS-triggered emphysema and pulmonary inflammation by targeting cellular senescence processes and modulation of Sp1/SIRT1/HIF-1α pathway.