Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is associated with chronic inflammatory response to noxious particles or gases. The airflow limitation may be explained by hypersecretion of mucus, thickening and fibrosis of small airways and alveolar wall destruction in emphysema. Sirtuins, a group of class III deacetylases, have gained considerable attention for their positive effects on aging-related disease, such as cancer, cardiovascular disease, neurodegenerative diseases, osteoporosis and COPD. Among the seven mammalian sirtuins, SIRT1-SIRT7, SIRT1 and SIRT6 are considered to have protective effects against COPD. In the lungs, SIRT1 inhibits autophagy, cellular senescence, fibrosis, and inflammation by deacetylation of target proteins using NAD(+) as co-substrate and is therefore linked to the redox state. In addition to SIRT1, SIRT6 have also been shown to improve or slow down COPD. SIRT6 is associated with redox state and inhibits cellular senescence and fibrosis. Therefore, activation of SIRT1 and SIRT6 might be an attractive approach for novel therapeutic targets for COPD. The present review describes the protective effects of SIRT1 and SIRT6 against COPD and their target proteins involved in the pathophysiology of COPD.