BACKGROUND: Renal complications of diabetes mellitus pose a significant public health challenge, contributing to substantial morbidity and mortality globally. Understanding temporal trends and regional disparities in mortality related to diabetic nephropathy is crucial for guiding targeted interventions and policy decisions. AIM: To display the trends and disparities of diabetic nephropathy related mortality. METHODS: A retrospective analysis was conducted using death certificate data from the center for disease control and prevention (CDC) wide-ranging online data for epidemiologic research analysis (WONDER) database, spanning from 1999 to 2020, to investigate mortality related to renal complications of diabetes in adults aged 35 or above. Age-adjusted mortality rate (AAMR) per 100000 persons and annual percent change (APC) were computed, with stratification by year, sex, race/ethnicity, and geographic region. RESULTS: Between 1999 and 2020, a total of 525804 deaths occurred among adults aged 35 to 85+ years due to renal-related issues associated with diabetes. AAMR for renal-related deaths in adult diabetic patients showed a consistent increase from 1.6 in 1999 to 34.9 in 2020 (average APC [AAPC]: 17.23; 95% confidence interval [CI]: 13.35-28.79). Throughout the study period, men consistently had higher AAMR (overall AAMR for men: 17.8; 95%CI: 17.7-17.9). In 1999, the AAMR for men was 1.8, increasing to 44.2 by 2020 (AAPC: 17.54; 95%CI: 13.09-29.53), while for women, it was 1.6 in 1999 and rose to 27.6 by 2020 (AAPC: 15.55; 95%CI: 13.35-21.10). American Indian/Alaska Native adults exhibited the highest overall AAMR (36.1; 95%CI: 35.2-36.9), followed by Black/African American (25.5; 95%CI: 25.3-25.7). The highest mortality was observed in the Western (AAMR: 16.6; 95%CI: 16.5-16.7), followed by the Midwestern region (AAMR: 14.4; 95%CI: 14.314.4). Significant variations in AAMR were observed among different states, with Oklahoma recording the highest (21.2) and Connecticut the lowest (7). The CDC WONDER database could potentially have omissions or inaccuracies. It does not provide data outside of the available variables. Furthermore, dataset after 2020 was not included in this study. CONCLUSION: Our findings highlight an alarming rise in mortality related to renal complications of diabetes among United States adults over the past two decades, with concerning disparities across demographic and geographic factors. These results underscore the urgent need for targeted interventions, policies, and protocols to address the growing burden of diabetic nephropathy and substantially reduce mortality rates in the United States. This will help improve the overall health outcome in the United States by identifying communities at risk and implementing tailored assistance to them.