Background: As the only effective treatment of celiac disease (CD) is a lifelong commitment to a gluten-free diet (GFD), this study was designed to evaluate the efficacy of GFD in the quality of life (QOL) of patients with CD to persuade them for strict commitment. Methods: In a cross-sectional study, the QOL of CD patients registered in the celiac society of Khuzestan province was evaluated and compared before and at least one year after commencing GFD using the QOL SF-36 questionnaire. Results: Overall, 200 CD patients (66 males and 134 females) were evaluated. The average age of male and female participants was 26.3 and 30.34 years, respectively (61% between 20 and 60-years-old). After GFD, complaints such as bloating (P = 0.001), abdominal pain (P = 0.001), diarrhea (P = 0.001), nausea (P = 0.001), vomiting (P = 0.03), reflux and regurgitation (P = 0.025), anorexia (P = 0.001), fatigue (P = 0.001), headache (P = 0.008), oral aphthous lesions (P = 0.014), weight loss (P = 0.001), and bone pain (P = 0.005) significantly improved while other symptoms such as muscular pain (P = 0.157), dermatitis (P = 0.083), and numbness (P = 0.317) did not show any major improvement. The average scores of QOL before and after GFD were 0.74 and 3.41, respectively, which demonstrated significant improvement (P = 0.001). This improvement was even seen among cases with sub-optimal compliance (average QOL score 3.28, P = 0.001). Conclusion: A gluten-free diet could significantly improve the quality of life of patients with celiac disease, and they should be encouraged as much as possible to be committed to this regimen.