Approximately 39 million people worldwide live with human immunodeficiency virus (HIV), and antiretroviral therapy (ART) has improved life expectancy for these individuals, with quality of life (QoL) being a crucial aspect. However, there is limited information on oral health-related quality of life (OHRQoL) for institutionalized patients with HIV. This study used a cross-sectional design and included 43 residents of a non-governmental institution who had a confirmed HIV diagnosis and a history of intravenous drug use. The Spanish version of the Oral Health Index Profile-14 (OHIPsp) was used to assess the OHRQoL, with the 50th percentile serving as the cutoff for good or poor quality of life. All 43 patients had one or more oral lesions, with 44.1% having AIDS-related oral lesions (AROLs). Over half of the participants (48.8%) reported a poor OHRQoL, and females experienced worse quality of life in all dimensions compared to males. Subjects with AROLs were three times more likely to have poor OHRQoL than those without AROLs (p = 0.03; OR = 3.1 _{IC 1.04–9.6}). These results highlight the need for a comprehensive treatment plan for patients with HIV that includes oral health, particularly for women living in precarious conditions or who are institutionalized. Improving oral health can significantly enhance quality of life.