Aim and Background: From past, study on the behavior and individual differences based on brain asymmetry is important in understanding of various disorders. Therefore, the aim of this study was comparing the difficulties of emotion regulation in patients with irritable bowel syndrome based on handedness.Methods and Materials: The present study was based on causative-comparative design. 30 right handedness and 30 left handedness patients among 120 patients with irritable bowel syndrome were selected by convenience sampling method that matched on gender, age and education level. The subjects completed two questionnaires: Edinburgh Handedness Inventory and Difficulties of emotion regulation scale (DERS). Data were analyzed using, Univariate Analysis of Variance (ANOVA) and Mann Whitney analysis.Findings: the results showed the mean score of left handedness patients in difficulties in emotional regulation was higher than right handedness patients (P<0.05). Between the two groups, among the subscales of emotional regulation difficulties, Difficulties engaging in goal directed behavior, Impulse control difficulties and Lack of emotional awareness had significant differences (P<0.05).Conclusions: The present study is a preliminary study in support of the role of emotion regulation in functional autonomic disorders such as irritable bowel syndrome.