There is a fine balance in maintaining healthy microbiota composition, and its alterations due to genetic, lifestyle, and environmental factors can lead to the onset of respiratory dysfunctions such as chronic obstructive pulmonary disease (COPD). The relationship between lung microbiota and COPD is currently under study. Little is known about the role of the microbiota in patients with stable or exacerbated COPD. Inflammation in COPD disorders appears to be characterised by dysbiosis, reduced lung activity, and an imbalance between the innate and adaptive immune systems. Lung microbiota intervention could ameliorate these disorders. The microbiota’s anti-inflammatory action could be decisive in the onset of pathologies. In this review, we highlight the feedback loop between microbiota dysfunction, immune response, inflammation, and lung damage in relation to COPD status in order to encourage the development of innovative therapeutic goals for the prevention and management of this disease.