Background: It has been established that the level of some inflammatory cytokines increases in CD and NCGS in comparison with healthy subjects. Therefore, the primary interest in our research was proposing an accurate tool to diagnose patients with CD and NCGS from healthy individuals in an Iranian population. Methods: The serum samples were examined in 171 participants, including 110 CD patients, 46 healthy individuals, and 15 NCGS. The commercial ELISA kits were used to detect the level of the following cytokines: IL-1, IL-6, IL-8, IL-15, and IFN-γ . The ROC curve analysis was applied to determine the optimal thresholds for high sensitivity, specificity, positive and negative predictive values of cytokines, as the indicators of CD, NCGS, and healthy control groups. Results: In NCGS group, the values of AUC for IL-1, IL-8, and IFN-γ were 71%, 78%, and 70%, respectively. To differentiate the CD and NCGS groups from the control group, IL-15 had the highest sensitivity (82. 70%), specificity (56. 50%), positive predictive value (81. 98%), and negative predictive value (57. 78%), followed by IL-8 with the highest sensitivity of 74. 50%, specificity of 73. 30%, and positive and negative predictive values of 95. 35% and 30. 21%, respectively. Conclusion: The obtained results demonstrate that IL-15 and IL-8 could be proposed as potential markers in their optimal cut-off points for distinguishing CD from the NCGS and the healthy control. Based on our findings, the evaluation of cytokine levels can be recommended as a useful tool for the diagnosis of CD and NCGS in a clinical practice.