(1) Background: Celiac disease (CD) is a common autoimmune disorder. The manifestations of the disease and the obligatory life-long gluten-free diet (GFD) are associated with the impairment of patients' quality of life. Therefore, the present study aimed to translate, culturally adapt and validate a celiac disease quality of life (CD-QoL) questionnaire and apply it to a representative number of Brazilian CD patients. (2) Methods: A cross-cultural Brazilian-Portuguese version of the CD-QoL was developed according to revised international guidelines. The questionnaire was administered to 450 celiac patients. The reliability, reproducibility and validity were studied. (3) Results: The Brazilian CD-QoL questionnaire presents valid measures of reproducibility and internal consistency. Early diagnosis is related to higher scores of Brazilian CD-QoL social, sub- and total scale. There was a positive correlation between higher education level and higher QoL. Individuals with partners tend to have a better emotional subscale of QoL. CD-patients who follow a strict GFD have highest QoL scale values. Men scored higher than women on the CD-QoL. All results were statistically significant except for the gastrointestinal subscale. (4) Conclusions: Brazilian CD-QoL allows comparative research between different celiac populations in the world. QoL research will help in the development of effective strategies to improve Brazilian celiac patients' quality of life.