Purpose <p>Poor sleep quality is common in adults with chronic diseases and may contribute to impaired oral health and reduced oral health-related quality of life (OHRQoL). The present study aimed to assess the association between sleep quality and OHRQoL in a large cohort of patients with chronic diseases.</p> Methods <p>This cross-sectional study used data from ComPaRe, a French e-cohort of adults with at least one chronic disease. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and OHRQoL with the Oral Health Impact Profile-14 (OHIP-14). Participants were categorized into PSQI quartiles. Associations between PSQI and OHRQoL were examined using correlation and multivariable linear regression adjusted for age, sex, body mass index, education, financial situation, marital status, smoking, number of missing teeth, and multimorbidity.</p> Results <p>A total of 10,759 participants were included. Only 23.6% had good sleep quality (PSQI ≤ 5). Mean OHIP-14 score increased progressively across PSQI quartiles, from 5.12 in the best sleep group to 11.80 in the worst sleep group (6.68-point difference). PSQI and OHIP-14 were positively correlated (Pearson <i>r</i> = 0.28, <i>p</i> &lt; 0.001). In multivariable analysis, each 1-point PSQI increase was associated with a 0.47-point increase in OHIP-14 score (95% CI: 0.468–0.478; <i>p</i> &lt; 0.001). Among all predictors included in the model, the number of missing teeth was the strongest determinant of OHRQoL (standardized β = 0.258), followed by PSQI score (standardized β = 0.210).</p> Conclusion <p>Poor sleep quality is significantly associated with poorer OHRQoL in patients with chronic diseases, highlighting the role of sleep in comprehensive oral and general health care.</p>