Background: Type 2 diabetes mellitus (DM2) can affect the quality of life of patients due to oral lesions related to the disease and that would impact their daily activities. Purpose: To estimate the impact of oral conditions and lesions on the health-related quality of life (OHRQoL) in patients with DM2 attending the MEDICUS Foundation in Cartagena, Colombia. Methods: An analytical study was conducted on 152 patients who filled out a questionnaire to assess sociodemographic variables and the General Oral Health Assessment Index (GOHAI-C), Colombian version. Two calibrated examiners performed the oral clinical assessment. Poisson regression was performed to associate oral clinical and socioeconomic conditions with the domains and total GOHAI score. Results: 74.34 % of the patients presented more than 5 years with diagnosed DM2. The multivariate adjusted model showed that patients with DM2 who presented low salivary flow (RR = 1.08; p < 0.001) and denture stomatitis (RR = 1.10; p = 0.001) were more likely to have a negative impact on total GOHAI scores. On the other hand, other oral lesions such as periodontitis (RR = 0.95; p = 0.046), geographic tongue (RR = 0.94; p = 0.013), sialosis (RR = 0.85; p < 0.000) and having <19 teeth in the mouth (RR = 0.94; p = 0.006) had a positive impact. Conclusions: Sub-prosthetic stomatitis and low salivary flow showed a negative impact on the OHRQoL of the Colombian patients with DM2 studied.