Background: Youth with Type 2 Diabetes (T2D) often develop early-onset kidney disease, with albuminuria as the initial biomarker. Psychological factors, including perceived stress, are associated with the progression of kidney disease, although the mechanisms remain unclear. This study investigated DNA methylation changes in youth with T2D and albuminuria compared to those without albuminuria and examined whether changes in DNA methylation existed in genes known to be associated with stress functions. Methods: This cross-sectional study analyzed data from 213 youth with T2D enrolled in the national iCARE cohort study. Kidney injury was assessed by non-orthostatic albuminuria, and perceived stress was measured using the PSS-14 questionnaire. Whole blood DNA methylation patterns were analyzed using an epigenome-wide association study (EWAS) to identify differentially methylated sites. Associations with albuminuria were tested with multiple linear regression models. A differentially methylated region (DMR) analysis explored broader DNA methylation differences across the genome in areas related to kidney injury. A candidate gene analysis compared CpG sites from our study to the EWAS Atlas, with significance assessed using t-tests. Results: Based on the EWAS, no significant sites were associated with albuminuria. Six significant DMRs were identified, corresponding to the genes: TNXB, TSPAN32, ZNF486, ZNF562, ATP5E, and TNFRSF6B. These genes are linked to energy metabolism, immune regulation, and extracellular matrix maintenance. In the candidate gene analysis, we identified 56 CpG sites with significant differences at a p-value < 0.05 and 18 sites at a p-value < 0.01. Conclusion/Importance: Although no significant site-level differences were found, the six significant DMRs suggest potential regions of epigenetic variation that could be associated with stress and kidney injury in youth with T2D. Given the exploratory nature of these findings and the limitations of bloodbased DNA methylation studies, further research is needed to clarify the role of DNA methylation changes. These findings may help guide future investigations into the role of epigenetics in kidney injury and stress in youth-onset T2D.