Background <p>25-hydroxyvitamin D [25(OH)D] is closely related to depressive symptoms and chronic kidney disease (CKD), especially in diabetic patients. This study aimed to determine whether elevated 25(OH)D could modify the association of depressive symptoms and CKD in diabetic patients. </p> Methods <p>We conducted a cross-sectional study, included diabetic patients from the National Health and Nutrition Examination Survey from 2007–2008 to 2017–2018. The Patient Health Questionnaire 9 (PHQ-9) indicates depressive symptoms. 25(OH)D was stratified according to the median (56.1&#xa0;nmol/L). Weighted logistic regression models were used to quantify the association between depressive symptoms and CKD. The model was adjusted for age, sex, race, education, smoking and alcohol status, and hypertension. As an exploratory analysis, we used the likelihood ratio test to calculate the interaction. Johnson-Neyman analysis was used to determine the 25(OH)D concentration at which significant and non-significant associations between depressive symptom and CKD occurred in linear models.</p> Results <p>This study included a total of 5196 diabetic patients. After adjusting for all confounding factors, PHQ-9 score ≥ 10 was independent risk factors for CKD (OR = 1.31, 95%CI 1.01–1.64). When 25(OH)D ≤ 56.1&#xa0;nmol/L, PHQ-9 score ≥ 10 was associated with CKD (OR = 1.65, 95%CI 1.22–2.23), but when 25(OH)D &gt; 56.1&#xa0;nmol/L, PHQ-9 score ≥ 10 was not associated with CKD (OR = 1.00, 95%CI 0.69–1.45). The interaction showed that elevated 25(OH)D modifies the association between depressive symptoms and CKD (P for interaction = 0.039). The modification concentration of 25(OH)D was 58.7&#xa0;nmol/L.</p> Conclusion <p>Elevated 25(OH)D modifies the relationship between depressive symptoms and CKD in diabetic patients.</p>