Pulmonary function testing, regarded as the "gold standard" for the classification and evaluation of therapeutic efficacy in chronic obstructive pulmonary disease (COPD), is a core method for its diagnosis and management. Among these tests, pulmonary ventilation parameters can effectively reflect the degree of airway obstruction; however, they are limited in detecting early lung parenchymal damage and microvascular lesions. In contrast, the diffusing capacity of the lung for carbon monoxide (DLCO) is an important indicator of pulmonary gas exchange function, which responds sensitively in the early stages of COPD and provides valuable clues for early disease detection. This article systematically discussed the role of DLCO in the early identification of COPD, assessment of disease severity, risk of acute exacerbations, long-term prognosis, and summarized its unique clinical value in COPD and related comorbidities. DLCO might serve as an alternative indicator for disease evaluation or prognostic assessment in patients with poor lung function or advanced age who were unable to complete pulmonary ventilation testing. Furthermore, in patients with COPD complicated by pulmonary hypertension, heart failure, or lung cancer, DLCO could effectively reflect the severity of comorbidities and assist in prognostic evaluation. This review provided a useful reference for future studies on DLCO in patients with COPD and its comorbid conditions.