Diabetes represents one of the main chronic diseases worldwide. Diabetes and its associated complications may be detectable even at early stages in the urinary proteome. In this article we review the current literature on urinary proteomics applied to the study of diabetes and diabetic complications. Further, we present recent data that strongly indicate urinary proteome analysis may be a valuable tool in detecting diabetes-associated pathophysiological changes at an early stage, and also may enable assessment of disease progression and efficacy of therapy. Current data indicate that collagen-derived peptides represent one of the main peptidic components in urine, which are consistently found at reduced levels in diabetes. It is tempting to speculate that this decrease in urinary collagen-derived peptides is related to an increase in extracellular matrix deposition which is a major complication in diabetes. Therefore, urinary proteome analysis might enable noninvasive assessment of this process at an early stage via determination of specific collagen fragments. This may open an avenue towards targeted therapeutic intervention.