Irritable bowel syndrome (IBS) is a heterogeneous and complex functional gastrointestinal disorder with a global prevalence of approximately 11% and high geographic variation. IBS encompasses various symptom clusters considered to reflect complex patho-etiological mechanisms, and effective treatment options are limited, with most medications targeting individual mechanisms and symptoms. Therefore, multi-targeted treatment is required. IBS is currently viewed as a disorder of disturbed gut-brain interactions with abnormalities at different sites along the gut-brain axis, including altered gastrointestinal motility, visceral hypersensitivity, increased intestinal permeability, and altered gut microbiota. All of these abnormalities represent individual targets for STW 5, a herbal preparation with nine different extracts indicated for the treatment of functional dyspepsia and IBS. As a multi-targeted medicinal drug, STW 5 possesses multiple pharmacodynamic effects. Several in vitro and in vivo studies have demonstrated STW 5 efficacy on numerous IBS patho-mechanisms targeting gastrointestinal smooth muscles, visceral afferent nerves, inflammation, gut permeability, and the gut microbiome.