Helicobacter pylori (HP) is a helical-shaped bacterium that inhabits the human stomach and is associated with various pathologies, including gastritis, gastric ulcers, and gastric cancer. HP infection is the largest contributor to gastric cancer, and approximately 90% of non-cardia gastric cancers are related to HP infection. As HP gastritis is an infectious disease, eradicating HP is an effective measure to prevent gastric cancer. Traditional triple therapy has demonstrated limited efficacy due to the emergence of antibiotic resistance and disruption of the intestinal microbiota. Sonodynamic therapy is an innovative nonantibiotic approach that utilizes a sonosensitizer to generate reactive oxygen species in response to ultrasound, effectively targeting pathogenic microorganisms; recent advancements have highlighted its potential for the treatment of HP infection. This article reviews recent developments in ultrasound-assisted biomaterials designed to combat HP while simultaneously preserving intestinal microecology. Furthermore, it discusses the integrated mechanisms underlying both the anti-HP effects and the maintenance of intestinal microecology. These strategies provide novel insights into overcoming the limitations associated with traditional antibiotic therapies and establish a foundation for future clinical applications.