Background <p>Chronic kidney disease and end-stage renal disease are significantly contributed by diabetes mellitus (DM), especially diabetes mellitus type 2 (T2DM). A stable surrogate marker of vasopressin, the serum copeptin, has become a potential biomarker of poor glycemic control and diabetic kidney disease (DKD). The research objective is to estimate the usefulness of the serum copeptin as a marker of glycemic status and its correlation with DKD in patients with T2DM.</p> Methods <p>This cross-sectional study was conducted on 60 participants at Cairo University Hospital between 2021 and 2022. Participants were divided into 40 T2DM patients (26 males, 14 females; mean age 52.62 ± 9.7 years) and 20 healthy controls. Diabetic patients were further categorized into controlled (HbA1c ≤ 7%, <i>n</i> = 18) and uncontrolled (HbA1c &gt; 7%, <i>n</i> = 22) subgroups. Clinical evaluation, biochemical tests, and serum copeptin levels (measured via ELISA) were analyzed. Cairo university, Faculty of Medicine, Ethical approval: N-247-2023.</p> Results <p>Serum copeptin levels were significantly higher in diabetic patients compared to controls (<i>p</i> &lt; 0.001), and in uncontrolled vs. controlled diabetics (<i>p</i> &lt; 0.001). Copeptin positively correlated with fasting glucose, HbA1c, serum creatinine, and urinary protein, and negatively with eGFR. ROC analysis identified copeptin as a sensitive marker for both poor glycemic control at a cut off value &gt; 3452 pg/mL (AUC 0.925) and DKD at a cut off vlue &gt; 370 pg/mL (AUC 0.94), both with high sensitivity and specificity.</p> Conclusion <p>The level of serum copeptin correlates positively with poor glycemic status as well as DKD among T2DM patients. It can be an effective, non-invasive biomarker used in early diagnosis and risk stratification of diabetic complications.</p> Clinical trial registration <p>Not applicable.</p>