The relationship between Helicobacter pylori infection and many extragastroduodenal manifestations remains a fascinating topic of investigation. Since the stomach is a large organ containing a potentially high bacterial load, H. pylori infection might elicit a spectrum of pathologic consequences beyond the gastroduodenal tract through either inflammatory mediator released into circulation or the host immune response. Currently, although for several proposed associations the potential pathogenic mechanism remains unclear, a bacterial involvement cannot be excluded. In the intestinal tract, an interaction between H. pylori and microbiota, with protective or aggressive outcome, could explain the features of several diseases. Inflammatory bowel disease (IBD), that comprises Crohn’s disease and ulcerative colitis, originates from a dysregulation of the host’s immune response to commensal bacteria in individuals with genetic predisposition. The reduction of biodiversity and other specific imbalances in the fecal microbiota composition of IBD patients compared to that of healthy controls support this hypothesis. In such a scenario, an inverse correlation between H. pylori infection and IBD prevalence has been confirmed worldwide. Growing interest in a potential role of H. pylori arises from studies investigating metabolic syndrome, a condition involved in the pathogenesis of cardiovascular diseases. Other reported fields of investigation are hepatology, with a particular focus on non-alcoholic fatty liver disease; neurology, including Parkinson’s disease and Alzheimer’s disease; and hematology as well as dermatology. The present narrative review highlights the main associations between H. pylori and extragastroduodenal manifestations published during the past year.