Diabetes Mellitus (DM) prevalence has been increasing, with over 415 million cases worldwide and a mortality rate of 2.5–5 million each year. Micronuclei (MN), which are cytoplasmic chromatin masses, have recently been suggested as a biomarker for cancer risk. An elevated micronuclei frequency is associated with DM. The oral cavity is considered a mirror reflecting an individual's health. This study aims to investigate the genotoxic effects of diabetes mellitus on human oral cells. This is a case-control study conducted in Shendi town from October 2021 to March 2022 at diabetic clinics. Forty-three mouth rinse samples were collected from diabetic patients and seventeen from non- diabetic individuals. All samples were centrifuged, and the sediment was smeared onto clean glass slides. It was then immediately fixed in 95% ethanol and stained with Papanicolaou stain and the Feulgen reaction to detect and calculate the rate of MN formation among the study groups. Data were analyzed using SPSS version 28.0. Cytology screening showed the MN rate among diabetics was 5.17 MN/100 cells with a standard deviation of 5.01, while among non- diabetics it was 2.29 MN/100 cells with a SD of 1.49. The difference between the two means was statistically significant (P-value 0.024). In this study, MN formation in diabetic patients' mucosal cells was correlated with control of DM (P-value 0.02) and metformin intake (P-value 0.045), but it was not correlated with either age or duration of the disease. Other cellular changes observed alongside micronuclei in diabetic oral mucosa included nuclear anomalies (95. 3%), hyperkeratosis /metaplasia (42%), inflammatory cells (76.7%), megalo-plastic changes (53.5%), nuclear atypia (72.1%), and binucleation (67.4%). No cellular anomalies were observed in non- diabetic oral cells. Papanicolaou stain demonstrated higher sensitivity (87.1%) for detecting MN formation and lower specificity (10%) compared to the Feulgen reaction. DM and its treatment with metformin exhibit a genotoxic effect on oral cells. The study recommends implementing oral cytology and genetic screening programs for diabetic patients, utilizing the Feulgen reaction as the most effective method for MN detection.