Oral health care may improve the health-related quality of life (HRQoL) of HIV/AIDS patients. We aimed to evaluate oral health and HRQoL of HIV/AIDS patients using antiretroviral therapy.A cross-sectional study included 120 HIV-infected patients, aged ≥18 years, from February, 2016 to September, 2017. The 36-Item Short Form Health Survey (SF-36) was used to evaluate the HRQoL. We assessed dental caries status using the Decayed, Missing and Filled Teeth (DMFT) index. Information about demographic, socioeconomic status, depression, and other comorbidities were collected. All patients with depression had a medical diagnosis. Comorbidities were defined as medical diagnoses of arterial hypertension, type-2 diabetes, tuberculosis, syphilis, cardiopathy, chronic renal failure, lymphoma, HCV infection, HBV infection and fatty liver disease. Independent t-tests were used to compare differences between mean levels of HRQoL, age, and DMFT and its components according to groups of sex, comorbidities and depression. Simple linear regression was used to analyze the relationship between the Mental Component Summary (MCS) and DMFT, and a multiple regression equation investigated depression, age, MCS, and comorbidities as predictors of DMFT.The mean DMFT index was 12.4 ± 8.2. A linear regression equation estimated a significant (p = 0.022) decrease of 0.25 unit (%) in MCS for each unit increase in DMFT. Among depressed patients, a significant (p = 0.008) decrease of 0.67% in MCS for each unity increase in DMFT was estimated. Depressed patients showed worse oral health indicators (DFMT index; p ≤ 0.001; and mean Missing Teeth; p ≤ 0.052) and lower HRQoL domains than non-depressed patients. DMFT remained associated with depression (P < 0.005) after controlling for age, MCS, and comorbidities.We found association between poorer oral health (higher DMFT index) and lower Mental Health Component Summary in HIV-infected patients with depression. Patients with depression deserve especial attention to their HRQoL and oral care.