Background: Living gluten-free is a well-known concept for children with celiac disease who need to be knowledgeable and closely adherent to a gluten-free diet (GFD) to ensure good health-related quality of life. The study was conducted to assess adherence to GFD, knowledge, and health-related quality of life of children with celiac disease. Subjects and Methods: a descriptive cross-sectional study was conducted on 103 children with celiac disease at the outpatient clinic of Gastroenterology and the Bakery for Special Therapeutic Nutrition at Zagazig University Hospitals. Data collection tools included; Leffler's questionnaire for adherence, GFD knowledge quiz, and celiac disease-specific pediatric health-related quality of life (CDPQOL). Results: Less than one-fifth of the studied celiac children reported excellent adherence to GFD and less than one-sixth of them had good knowledge about GFD. Low total health-related quality of life scores were found in about three-fifths of children aged 8-12 years and nearly half of adolescents aged 13-18 years. Furthermore, adherence to GFD showed a significant positive correlation with health-related quality of life. Conclusions: Children with celiac disease had poor knowledge about GFD and poorly adhered to it. They also reported low health-related quality of life that was affected by poor adherence to GFD. Recommendations: Continuous evaluation of children's adherence to GFD and discussion of children's beliefs and concerns about dietary regimens should be done routinely. Also, tailored multifaceted interventions designed to meet the needs of children with celiac disease would help manage adherence.