Objective <p>To investigate the prevalence of depression and anxiety in interstitial lung disease (ILD) and reveal whether ILD is causally associated with depression and anxiety via Mendelian randomization (MR).</p> Methods <p>Eligible studies were identified and selected from Web of Science, PubMed and Scopus. The pooled prevalence of depression and anxiety in ILD, as well as the clinical characteristics of ILD with depression or anxiety, were assessed. Sensitivity analyses, subgroup analyses and meta-regression were applied for heterogeneity assessments. Data of MR analysis were derived from the UK biobank and Finngen cohort, and the inverse variance weighting approach was selected as the main approach for causality evaluation.</p> Results <p>A total of 35 studies were included in this meta-analysis, with 34 studies reporting depression in ILD and 21 reporting anxiety in ILD. The pooled prevalence of depression and anxiety in ILD were 22% (95% CI 17%, 26%, I² = 97%) and 25% (95% CI 18%, 32%, I² = 98%), respectively. There was no significant difference in the prevalence of depression (p = 0.41) or anxiety (p = 0.39) across various subtypes of ILD. ILD patients with depression had a lower BMI (MD −2.11, 95% CI −3.82, −0.41, p = 0.02). Results of MR analysis revealed no causal associations for either the ILD-depression (OR 1.000, 95% CI 0.997, 1.003; p = 0.962) or the ILD-anxiety (OR 1.000, 95% CI 0.998, 1.002; p = 0.888) relationships.</p> Conclusion <p>Although the prevalence of depression and anxiety were high in patients with ILD, no causal relationship was observed. Future studies are needed to investigate the intricate association between ILD and mental health.</p>