Oral potentially malignant disorders (OPMD) refer to a group of diseases occurring on the oral mucosa that harbor the potential to progress into oral squamous cell carcinoma, including oral leukoplakia, oral erythroplakia, discoid lupus erythematosus of the oral mucosa, oral submucous fibrosis, oral lichen planus, actinic cheilitis, etc. Diabetes mellitus (DM) is one type of diseases characterized by chronic hyperglycemia, with a high incidence and mortality rate worldwide. Hyperglycemia is the characteristic metabolic change in DM patients and those in the pre-diabetic stage, playing a determinative role in many complications related to DM. A number of clinical studies had revealed an association between hyperglycemia and OPMD, as well as its malignant transformation. This article will review the potential regulatory effects and mechanisms of high glucose states, such as diabetes, on OPMD, and assess the correlation between hyperglycemia and the malignant transformation of OPMD.