Introduction The pathogenesis of diabetic nephropathy highlights the progression of inflammation and fibrosis from tubular to glomerular damage during the early stages of kidney involvement in diabetic individuals. As urine albumin serves as a marker for glomerular function, its detection indicates a stage of diabetic nephropathy where the glomerulus is already compromised. Consequently, relying solely on urine albumin for diagnosis becomes questionable. In our pursuit of identifying innovative biomarkers for the early detection of diabetic nephropathy, this study was crafted to explore the relationship between chemokines, omentin-1, interleukin-6, and microalbuminuria. Materials and methods Our study cohort comprised 116 patients diagnosed with diabetes mellitus. In our study, participants were stratified into two groups based on their urine albumin levels: Group 1, characterized by urine albumin creatinine ratio <30 mg/gm and estimated glomerular filtration rate >90 ml/min, and Group 2, with urine albumin creatinine ratio ≥30 mg/gm and <300 mg/gm, and estimated glomerular filtration rate >60 ml/min and <90 ml/min.Serum creatinine, glycated hemoglobin (HbA1c), fasting blood sugar and post-prandial blood sugar, lipid profile, total protein, albumin, fasting insulin, omentin-1, and interleukin-6 were estimated. Result There was a significant difference in the medians of serum urea, creatinine, omentin-1, interleukin-6, urine albumin creatinine ratio, and estimated glomerular filtration rate levels in the two groups. There was no difference in fasting blood sugar, post-prandial blood sugar,HbA1c, serum lipids, fasting insulin, and homeostatic model assessment for insulin resistance. The receiver operating characteristic curve plotted for the newer biomarkers of diabetic nephropathy showed that there was a significant diagnostic utility in diabetic nephropathy detection of serum omentin (p=0.000), interleukin-6 (p=0.002), and interleukin-6: omentin-1 ratio (p=0.000), which correlated well with the routine test that is urine microalbumin estimation. Risk assessment demonstrated that type 2 diabetes mellitus patients with an interleukin-6: omentin-1 ratio ≥0.26 had significantly higher odds, with an odds ratio of 3.97, for developing diabetic nephropathy, which was statistically significant. Conversely, a ratio of ≤0.26 was associated with kidney protection among patients with type 2 diabetes mellitus. Conclusion Our findings revealed decreased levels of omentin-1 and increased levels of interleukin-6 in the group with diabetic nephropathy compared to those without diabetic nephropathy among patients with type 2 diabetes mellitus. Interleukin-6: omentin-1ratio of ≤0.26 was associated with kidney protection among patients with type 2 diabetes mellitus. Based on the results obtained from this study, we propose that measuring the serum interleukin-6: omentin-1 ratio in patients with type 2 diabetes mellitus may assist in identifying the early stages of diabetic nephropathy before the onset of microalbuminuria. Timely intervention in these patients predisposed to diabetic nephropathy can aid in better treatment outcomes in type 2 diabetes mellitus.