The gut-brain axis is a bidirectional communication system that exists between the brain and gut.Several studies claimed that some types of headaches are associated with various gastrointestinal (GI) disorders.In Persian medicine (PM),physicians believed that gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache.Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM.Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks.PubMed,Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants.A total of 24 plants were recorded from the selected sources included in this review,most of which belonged to the Rosaceae family.Phyllanthus emblica,Zingiber officinale,Boswellias errata,Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache,while current research about quince,rose,apple,hawth and pear was limited.Reducing Helicobacter pylori growth,gastritis,erosion of the stomach lining,hemorrhage and perforation,improving gastric mucosal resistance,antisecretary,antiulcer,antipyretic,analgesic,sedative,anxiolytic,anti-inflammatory,anticonvulsant,neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research.These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities.However,further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants.