Comprehensive treatment is crucial for patients with a cleft lip/palate. While studies have investigated its impact on children's quality of life, few have examined the effects on primary caregivers. The aim of the study was to compare the quality of life of caregivers of children with cleft lip/palate to a control group at the National School for Higher Studies, National Autonomous University of Mexico, Guanajuato. A cross-sectional study was conducted at a teaching dental clinic of the National School of Higher Studies, National Autonomous University of Mexico, Guanajuato, México, from May to December 2021 involving 140 caregivers (70 in each group). The WHOQoL Bref instrument assessed the quality of life. In addition to the descriptive analysis, a binary logistic regression analysis was carried out, taking dichotomized reported quality of life as the dependent variable. Among the caregivers, 88.6% were female ( > 0.05), and 45 (64.8%) from the study group reported poor quality of life ( < 0.05). A multivariate analysis indicated that caring for a child with cleft lip/palate raised the likelihood of poor quality of life ( < 0.05). The findings emphasize the need for comprehensive support for both patients and caregivers, as their well-being affects patient outcomes.