Background Sleep is integral to cardiometabolic health. While there is emerging evidence linking sleep-related leg movements (SRLM) to diabetes mellitus (DM), the underlying mechanisms remain unclear. This study investigates the association between SRLM and DM prevalence in a national population-based cohort study in the United States (US), considering potential mediators like short sleep duration and inflammation and examining variations across age, sex, and race/ethnicity. Methods We analyzed data from 9,191 adults (aged ≥18 years) from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. We assessed the frequency of SRLM (leg jerks and leg cramps) and diabetes prevalence (self-reported diagnosis, diabetes medication use, or glycosylated hemoglobin (HbA1c) ≥ 6.5%). Weighted logistic regression models were used to evaluate the associations, adjusting for demographic and clinical-related confounders. Mediation analyses were conducted to explore the roles of short sleep duration and inflammation (C-reactive protein levels). Results The study revealed that 1,278 (14%) participants have DM. SRLM was associated with a 72% increase in the odds of diabetes (OR=1.72, 95% CI: 1.06-2.81). The association is more pronounced in non-Hispanic White individuals, females, and adults aged 18-65. Short sleep duration and inflammation mediated 5.0% and 3.9% of this association, respectively. Conclusions SRLM is independently and linearly associated with increased prevalence of diabetes in a representative sample of the US adult population. Short sleep duration and inflammation mediated a small part of this association. Confirming the association in other samples and further investigation into its mechanisms are warranted to better understand the roles of the SRLM in the risk of diabetes.