Diabetic kidney disease is a serious complication of uncontrolled diabetes. In this context, more than 50% of the patients on dialysis have diabetes as their primary cause of kidney failure. Diagnostic markers to detect diabetic kidney disease even before the onset of albuminuria is important to guide early intervention to slow the progression of diabetic kidney disease. Both serum and urinary biomarkers may be elevated before the appearance of albuminuria in the diabetic population and they can be used for detection of early diabetic kidney disease. As diabetes effect glomeruli, tubules and vessels in the kidney, the biomarkers can broadly be divided into those derived from glomerular or tubular injury. Further, inflammatory biomarkers are also useful in the early detection of diabetic kidney disease. Detection of these biomarkers can identify the diabetic kidney disease even before the onset of albuminuria. Further response of these biomarkers to our treatment can govern the management strategies in this complicated group of patients. Despite the identification of various useful markers, further large, multicenter prospective trials are still needed to confirm their clinical usefulness. This chapter will discuss novel biomarkers of diabetic kidney disease and new applications of these markers for early detection and progression of disease.