Background: We performed a systematic review of studies conducted in Latin America and the Caribbean (LAC) to assess the impact of oral diseases on oral health-related quality of life (OHRQoL). Materials and methods: Searches were performed of the following PubMed, EMBASE, CINAHL, Scopus, and LILACS databases. Randomized clinical trials, quasi-experimental studies, cohort studies, case and control studies, and cross-sectional studies which included at least 100 participants evaluating the impact of oral diseases on OHRQoL were included. PROSPERO registry number: CRD42020156098. Results: After exclusion of duplicates, 3310 articles were identified, 40 of which were included in this review. 90% of the studies were conducted in Brazil. The most commonly used OHRQoL measuring instruments were CPQ 11-14 (n = 9), ECOHIS (n-8) and B-ECOHIS (n = 8). The study designs included 32 cross-sectional, 2 cohort and 6 case and control studies. Most of the studies were conducted in children (n = 25) and adolescents (n = 9). Most studies identified an impact on OHRQoL in children, adolescents and adults with oral diseases. Moreover, greater oral disease severity had a greater impact on OHRQoL. Conclusions: Most studies in LAC report a negative impact of diseases on OHRQoL. More longitudinal studies are required to confirm the results of these studies.