Helicobacter pylori (H. pylori) infection have been closely associated with several extra-gastrointestinal disorders. Outer membrane vesicles (OMVs), as lipid-membrane-bounded nanoparticles, are usually shed from Gram-negative both in vitro and in vivo. H. pylori is also capable of producing OMVs, which can enter the systemic circulation and be delivered to various cells, tissues or organs, eliciting a range of inflammatory and immune modulation responses. In this current review, we summarize the biogenesis and functions of H. pylori OMVs, describe the contribution of H. pylori OMVs to the generation and progression of extra-gastrointestinal diseases, such as neuronal damage, Alzheimer disease, hepatic fibrosis and atherosclerosis. We also explored the effect of H. pylori OMVs in inflammatory and immune modulation of diverse immune cells, including macrophages, mononuclear cells and dendritic cells. By elucidating the molecular mechanism of H. pylori OMVs-mediated extra-gastrointestinal diseases and immunomodulatory effect, it may promote the development of efficient treatments and vaccinations against H. pylori.