Chronic obstructive pulmonary disease (COPD) is a multifactorial condition characterized not only by damage to the respiratory system but also by pronounced systemic manifestations, including endothelial dysfunction, oxidative stress, and comorbidities. Cardiovascular and renal complications, driven by shared pathogenetic mechanisms such as chronic inflammation, hypoxia, and microcirculatory disorders, have the greatest clinical significance. This review presents current insights into the pathogenesis of COPD in the context of comorbidity, with an emphasis on the role of systemic inflammation, endothelial dysfunction, and activation of free radical processes. Both pharmacological and non-pharmacological treatment approaches are discussed, including bronchodilators, inhaled corticosteroids, phosphodiesterase-4 inhibitors, antioxidants, antihypoxants, as well as risk factor modification measures and pulmonary rehabilitation. Special attention is given to the interplay between COPD and chronic kidney disease, as well as the prospects for combined therapeutic strategies aimed at correcting systemic disorders and improving patient outcomes. The presented data highlight the need for a comprehensive approach to COPD management, taking into account the individual course of the disease and associated comorbidities.