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<i>Aim:</i> This study was conducted to evaluate the impact of complementary and alternative medicine (CAM) in patients with irritable bowel syndrome (IBS) as assessed by the Rome IV criteria. <i>Methods:</i> Consecutive patients referring for IBS were re-evaluated according to the Rome IV criteria. Demographic features and characteristics potentially associated with the use of CAM were collected. A validated, self-administered, survey questionnaire dealing with CAM and patients&#8217; level of knowledge, motivation, perception, and information seeking-behavior toward the use of CAM was analyzed. Multivariate logistic regression analysis was performed in order to identify predictors of CAM use among participants. <i>Results:</i> Among 156 patients claiming IBS, 137 (88%) met the Rome IV criteria, and 62 of them (45%) were CAM users. Biologically based therapy was the most chosen CAM (78%). Significant risk factors (adjusted odds ratio, 95% confidence interval) for the use of CAM were female gender (7.22, 2.31&#8315;22.51), a higher BMI (1.16, 1.02&#8315;1.33), and a good knowledge of CAM (4.46, 1.73&#8315;11.45), while having children was a protective factor (0.25, 0.07&#8315;0.95). Only 19% of patients used CAM due to medical advice and over half (51%) thought it was a &#8220;more natural&#8222; approach. Although a minority of patients (16%) had full satisfaction from CAM, 81% of users would repeat the CAM experience for their IBS symptoms. <i>Conclusions</i>: The widespread use of CAM in IBS, the patients&#8217; belief in its safety, and their willingness to re-use it suggest that knowledge of health-care providers and patient education should be improved.