Depression is a common mental disorder and the leading cause of disability in the worldwide. Based on Islamic resources, indigestion and dyspepsia can lead to depression. In modern medicine, though many somatic diseases have been named as possible causes of depression, the effect of gastrointestinal disorders on depression is still an enigma. Therefore, the focus of this study is to explore the available scientific literature of modern medicine in order to find the footprint of effect of indigestion on depression. In this study, related articles were retrieved from PubMed, Ovid, Proquest and Magiran databases by using the Medical Subject Heading keywords "depression," "psychology," "dyspepsia" and "gastrointestinal diseases." In the next step, studies, which are exactly confirm the Islamic viewpoint, were selected from the retrieved articles. Only one prospective study in 2012 has stated that people with functional gastrointestinal disorders and without elevated levels of anxiety and depression at baseline had significantly higher levels of anxiety and depression at 12-year follow-up. Based on Islamic viewpoint, indigestion can lead to depression, but this aspect approved by only one 12-year prospective population-based study in our review. It seems that it is necessary to conduct complementary studies investigating this hypothesis.