Introduction <p>Gastrointestinal diseases and depression represent significant public health burdens among middle-aged and older women. This study investigated the association between gastrointestinal diseases and depression severity in Chinese women aged ≥ 45 years, and examined sleep duration as a potential mediator.</p> Methods <p>We performed a cross-sectional analysis of 6,433 women (aged ≥ 45) from the CHARLS database. Multivariable logistic regression evaluated the association between depression severity and gastrointestinal diseases, adjusting for confounders. Restricted cubic spline (RCS) models assessed nonlinear trends. Additionally, correlation and subgroup analyses were conducted to evaluate the consistency of this relationship across different population strata. Mediation analysis with nonparametric bootstrapping quantified sleep duration’s indirect effect.</p> Results <p>Among these women, the prevalence of gastrointestinal diseases was 24.8%, and that of depression was 43.7%. Both depression severity and reduced sleep duration showed significant associations with gastrointestinal diseases (<i>p</i> &lt; 0.001). Each interquartile-range increase in depression score linked to an 11% higher risk of gastrointestinal diseases (OR: 1.11, 95% CI: 1.09–1.13). RCS analysis demonstrated a nonlinear relationship (<i>p</i> for non-linearity = 0.02), with risk accelerating when depression scores exceeded 8. Participants with scores of 20 had a 2.76-fold higher risk compared to those with scores of 9 (95% CI: 2.16–3.64). Sleep duration mediated 9.81% of the total association (<i>p</i> &lt; 0.001).</p> Conclusion <p>Our findings indicate a positive association between depression severity and gastrointestinal diseases, while sleep duration exhibited a negative association in this population. Moreover, sleep duration played a mediating role in the relationship between depression and gastrointestinal diseases.</p>