Background Adherence to a gluten-free diet (GFD) and food insecurity (FI) may influence health-related quality of life (HRQOL) in individuals with celiac disease (CD). This study aimed to investigate the association between adherence to a GFD, FI, and HRQOL in individuals with CD. Methods This cross-sectional study included 97 adults (mean age: 34 ± 9 years) diagnosed with CD. The participants were on a GFD for more than 6 months. Sociodemographic characteristics and medical history were assessed. Adherence to a GFD, FI, and HRQOL were assessed using validated questionnaires. Results Most participants (73%) adhered to a GFD, and 62% were experiencing FI. Individuals with CD faced difficulty in accessing GF foods due to the high cost (90%) and limited availability (79%). The mean overall HRQOL score was 60. Scores on the physical and mental health domains were 69 and 47, respectively. Adherence to a GFD was significantly associated with FI (P = 0.02), while there was no association between adherence to a GFD and HRQOL measures (P > 0.05). Participants facing FI had lower scores in emotional well-being and mental health domains, and overall HRQOL (P < 0.05). Conclusions The findings of the present study demonstrate that FI influences adherence to a GFD, and that FI is associated with HRQOL in terms of both emotional well-being and mental health.