<p>Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease and is pathologically associated with epithelial-mesenchymal transition (EMT) and mitochondrial dysfunction. Asiaticoside (AS) has shown significant anti-inflammatory effects in a variety of diseases. Herein, the pharmacological influences of AS in COPD were probed. COPD mice were exposed to cigarette smoke (CS), and BEAS-2B cells were treated with cigarette smoke extract (CSE) for in vitro studies. HE staining was performed to assess lung pathological alters. The role of AS on inflammation, apoptosis, EMT, and mitochondrial dysfunction was analyzed by ELISA assay, western blot, Flow cytometry, DCFH-DA staining, and JC-1 staining. TRIM27 m6A expression was measured by MeRIP assay. The relationship between YTHDF1, TRIM27, and PGC-1α was determined by Co-IP or RIP assays. AS treatment relieved CSE-triggered inflammation, apoptosis, EMT, and mitochondrial dysfunction in a dose-dependent manner. Mechanically, AS suppressed PGC-1α ubiquitination degradation by reducing TRIM27 level in an m6A-YTHDF1-dependent manner. As expected, the mitigatory effect of AS on CSE-triggered BEAS-2B cell damage was abrogated by TRIM27 addition. Further, TRIM27 addition abrogated the restoring effect of AS on CS-caused pulmonary pathological damage in COPD mice. AS alleviated COPD by activating PGC-1α/Nrf2 signaling through weakening TRIM27 stability in an m6A-YTHDF1-dependent manner.</p>