Celiac disease (CD) is an autoimmune disorder whose management relies mainly on a strict gluten-free diet (GFD). This cross-sectional study, conducted on 100 Tunisian patients between October and December 2023, assessed the impact of CD on quality of life (QOL) using a generic questionnaire (the SF-12) and a specific questionnaire (the CDQ). The results show that CD significantly alters QoL, with low scores in both physical and mental domains. Factors associated with impaired HRQOL included non-university education and low socio-economic status. The study recommends the systematic use of HRQOL assessment tools and the implementation of supportive strategies to improve RSG adherence and patient management.