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The effects of propolis, a well-known functional food, on irritable bowel syndrome (IBS), a chronic gastrointestinal disorder, in humans have yet to be investigated. This study evaluated propolis effects in IBS subjects. In this clinical study, 56 patients with IBS diagnosed by Rome IV criteria were assigned for 6 weeks randomly to the study groups. At the baseline and endpoint phase, patients’ gastrointestinal symptoms, quality of life (QOL), anxiety state, dietary intakes, and anthropometric indices were assessed. Independent t-test, paired t-test, Mann-Whitney U test, Wilcoxon, Fisher's exact test, repeated measures analysis of variance and logistic regression test were used for analyzing the data. To adjust the effect of confounders, covariance analysis was used. The results of this study showed that after modulating the effect of potential confounders, propolis supplementation increased the chance of improving IBS severity by 6.22 (with a con dence interval of: 1.33-1.14 and P= 0.035). A signi cant abdominal pain improvement, anxiety state, and bowel habits dissatisfaction reduction was observed within-and between-group differences in propolis group compared to the placebo group (P= 0.040, P= 0.035, P= 0.029, retrospectively). The overall score of quality of life and its domains in the propolis group was statistically signi cant, but in comparison between the two groups, this difference was not signi cant. Also, regards to the food intakes and anthropometric indices, there were no signi cant differences between and within the two study groups. This study illustrated that propolis supplementation could be used as adjunctive therapy in IBS disease to …