BACKGROUND Irritable bowel syndrome (IBS) is the most common chronic gastrointestinal (GI) disorder. Patients with IBS usually suffer from anxiety and depression. A combination of psychological approaches and pharmacological treatments can be a significantly effective treatment for IBS. The main objective of the present study was to provide a therapeutic plan based on laughter yoga and anti-anxiety medication, employed for the very first time, and to determine the effectiveness of these treatments on the anxiety and GI symptoms of patients with IBS. METHODS In this randomized, controlled, clinical trial, the participants were 60 patients selected from those who referred to the GI clinic of Vali-asr Hospital (Birjand, Iran) during the study period (April 2017 to March 2017) and were diagnosed as having IBS based on ROME III criteria. The participants were randomly assigned to either the laughter yoga group, the anti-anxiety medication group, or the symptomatic treatment (control) group. Severity levels of anxiety and GI symptoms before and after intervention were determined and compared among these three groups according to approved protocols. RESULTS The severity of IBS symptoms after the interventions was more greatly reduced in the laughter yoga group than in the anti-anxiety medication and control groups (p = 0.006). The severity of anxiety after interventions decreased in all three groups, especially in the yoga treatment group, but the difference was not statistically significant (p = 0.1). CONCLUSION Laughter yoga is more effective than anti-anxiety medication in reducing the GI symptoms of patients with IBS. Therefore, applying laughter yoga along with common pharmacological therapies for patients with IBS might be strongly advised.