This study explores the association between diabetes mellitus, systemic inflammation, and overactive bladder (OAB) in the general adult population in the United States. Using data from six cycles of the National Health and Nutrition Examination Survey (NHANES) 2007–2018, the study analyzed the relationship between diabetes-related markers, inflammatory biomarkers, and OAB. Logistic regression models were used to assess the association between diabetes, diabetes-related markers, and inflammatory biomarkers with OAB. Restricted cubic splines were used to analyze non-linear associations, and mediation analysis was performed to test the effect of inflammatory biomarkers on the relationship between diabetes-related markers and OAB. Machine learning models were also applied to predict the relative importance of these factors. The study found that the prevalence of OAB in individuals with diabetes was significantly higher than in non-diabetic individuals. As the quartiles of diabetes-related markers increased, the odds of OAB increased in all models. Glycohemoglobin showed a linear association with OAB, while fasting glucose and insulin showed non-linear associations. White blood cells and neutrophils significantly mediated the association between diabetes-related markers and OAB. Machine learning analysis showed that glycohemoglobin was the most important indicator for predicting OAB. The study also found that systemic inflammation played an important role in the association between diabetes and OAB. Mediation analysis showed that white blood cells and neutrophils were significant mediators of the association between diabetes-related markers and OAB. The study concluded that diabetes mellitus and diabetes-related markers were significantly associated with OAB, and systemic inflammation was an important mediator of this association. The findings suggest that diabetes may increase the risk of OAB by promoting systemic inflammation. The study highlights the importance of considering systemic inflammation in the management of OAB in diabetic patients.This study explores the association between diabetes mellitus, systemic inflammation, and overactive bladder (OAB) in the general adult population in the United States. Using data from six cycles of the National Health and Nutrition Examination Survey (NHANES) 2007–2018, the study analyzed the relationship between diabetes-related markers, inflammatory biomarkers, and OAB. Logistic regression models were used to assess the association between diabetes, diabetes-related markers, and inflammatory biomarkers with OAB. Restricted cubic splines were used to analyze non-linear associations, and mediation analysis was performed to test the effect of inflammatory biomarkers on the relationship between diabetes-related markers and OAB. Machine learning models were also applied to predict the relative importance of these factors. The study found that the prevalence of OAB in individuals with diabetes was significantly higher than in non-diabetic individuals. As the quartiles of diabetes-related markers increased, the odds of OAB increased in all models. Glycohemoglobin showed a linear association with OAB, while fasting glucose and insulin showed non-linear associations. White blood cells and neutrophils significantly mediated the association between diabetes-related markers and OAB. Machine learning analysis showed that glycohemoglobin was the most important indicator for predicting OAB. The study also found that systemic inflammation played an important role in the association between diabetes and OAB. Mediation analysis showed that white blood cells and neutrophils were significant mediators of the association between diabetes-related markers and OAB. The study concluded that diabetes mellitus and diabetes-related markers were significantly associated with OAB, and systemic inflammation was an important mediator of this association. The findings suggest that diabetes may increase the risk of OAB by promoting systemic inflammation. The study highlights the importance of considering systemic inflammation in the management of OAB in diabetic patients.