Aim and objective: This study aimed to investigate the impact of oral health on the quality of life of drug addicts in rehabilitation. Materials and methods: A total of 398 male individuals admitted to two drug rehabilitation centers between 2013 and 2016 responded to a structured questionnaire including sociodemographic, oral health habits, and drug usage variables. Respondents were also examined for dental caries. Oral health-related quality of life was measured using the Oral Health Impact Profile, in short-form, the OHIP-14. Descriptive statistical analysis, Mann–Whitney test, univariate and multiple Poisson regression with robust variance were performed using Stata/SE 14.1. Results: The mean severity score was 22.8 (SD = 13.2). The prevalence of worse impact (higher OHIP-14 scores) was 84.9%. In the univariate analysis, <8 years of schooling, no brushing teeth, self-perceived metallic taste, self-perceived tooth mobility, use of lysergic acid diethylamide (LSD) and oxy, missing teeth, and DMFT score >10 were associated with a negative outcome (p < 0.05). After adjustment, remained independently associated low schooling (p = 0.021) and self-perceived metallic taste (p < 0.001). Conclusion: Drug users perceived negatively the impacts of oral health-related quality of life. Clinical significance: Drug addicts have poor oral health and quality of life. Thus, public health strategies for the rehabilitation of these individuals should account for the biopsychosocial aspects.