BackgroundDiffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) can provide quantitative parameters that show promise for evaluation of diabetic kidney disease (DKD). The combination of radiomics with DTI and DKI may hold potential clinical value in detecting DKD.PurposeTo investigate radiomics models of DKI and DTI for predicting DKD in type 2 diabetes mellitus (T2DM) and evaluate their performance in automated renal parenchyma segmentation.Study TypeProspective.PopulationOne hundred and sixty‐three T2DM patients (87 DKD; 63 females; 27–80 years), randomly divided into training cohort (N = 114) and validation cohort (N = 49).Field Strength/Sequence1.5‐T, diffusion spectrum imaging (DSI) with 9 different b‐values.AssessmentThe images of DSI were processed to generate DKI and DTI parameter maps, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). The Swin UNETR model was trained with 5‐fold cross‐validation using 100 samples for renal parenchyma segmentation. Subsequently, radiomics features were automatically extracted from each parameter map. The performance of the radiomics models on the validation cohort was evaluated by utilizing the receiver operating characteristic (ROC) curve.Statistical TestsMann–Whitney U test, Chi‐squared test, Pearson correlation coefficient, least absolute shrinkage and selection operator (LASSO), dice similarity coefficient (DSC), decision curve analysis (DCA), area under the curve (AUC), and DeLong's test. The threshold for statistical significance was set at P < 0.05.ResultsThe DKI_MD achieved the best segmentation performance (DSC, 0.925 ± 0.011). A combined radiomics model (DTI_FA, DTI_MD, DKI_FA, DKI_MD, and DKI_RD) showed the best performance (AUC, 0.918; 95% confidence interval [CI]: 0.820–0.991). When the threshold probability was greater than 20%, the combined model provided the greatest net benefit. Among the single parameter maps, the DTI_FA exhibited superior diagnostic performance (AUC, 887; 95% CI: 0.779–0.972).Data ConclusionThe radiomics signature constructed based on DKI and DTI may be used as an accurate and non‐invasive tool to identify T2DM and DKD.Level of Evidence2Technical EfficacyStage 2