Background <p>Chronic obstructive pulmonary disease (COPD) is a major global health burden, with emerging evidence implicating gut microbiota dysbiosis via the gut-lung axis. The Dietary Index for Gut Microbiota (DI-GM) quantifies dietary impact on microbial health, but the mechanisms linking DI-GM to COPD risk remain unclear. This study aimed to investigate whether systemic inflammatory-nutritional biomarkers might explain the association between DI-GM and COPD, with a focus on the red cell distribution width-to-albumin ratio (RAR).</p> Methods <p>This cross-sectional analysis included 20,487 U.S. adults aged ≥ 40 years from the National Health and Nutrition Examination Survey (2005–2018). DI-GM was derived from 24-hour dietary recalls, and COPD was defined by self-reported physician diagnosis. Survey-weighted multivariable logistic regression and mediation analysis were used to assess associations and statistically decompose the potential mediating effects of 11 inflammatory-nutritional biomarkers.</p> Results <p>Each one-unit increase in DI-GM was associated with an 8% reduction in COPD prevalence (odds ratio 0.92, 95% confidence interval 0.88–0.97). In the mediation analysis, RAR was the most robust factor, accounting for 10.3% of the observed total association. Other biomarkers, including the neutrophil percentage-to-albumin ratio and monocyte-to-albumin ratio, showed significant but weaker contributions. These findings were consistent in sensitivity analyses.</p> Conclusions <p>Adherence to a gut microbiota-beneficial diet is associated with reduced COPD risk, and this association may be partially explained by systemic inflammatory-nutritional status. RAR emerged as a significant intermediary factor in this observed association, providing epidemiological clues for the gut-lung axis and suggesting its potential as a biomarker for further investigation in targeted prevention strategies.</p>