Depression is a prevalent disorder among patients suffering from irritable bowel syndrome. The current study was performed to evaluate the effect of a traditional Persian medicine product, anise oil, in removing the symptoms of mild to moderate depression in patients with irritable bowel syndrome. In a randomized double-blinded active and placebo controlled clinical trial, 120 participants with mild to moderate depression according to the Beck Depression Inventory–II total scores were categorized into 3 equal groups and received anise oil, Colpermin, and placebo. The results at the end of trial (week 4) and follow-up (week 6) demonstrated significant priority against active and placebo groups. Although the mechanism is unknown yet, anise oil could be a promising choice of treatment for depressed patients with irritable bowel syndrome.