Abstract: Helicobacter pylori (Hp) is a Gram-negative bacterium. Its infection can cause common gastrointestinal diseases such as chronic gastritis and peptic ulcer, and long-term persistent infection is closely associated with the occurrence and development of gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. The genome of Hp exhibits high polymorphism and genetic diversity, which is mainly driven by its high mutation rate, elevated gene recombination frequency, and complex dynamically regulated methylome. The pathogenicity of Hp strains is closely correlated with the sequence heterogeneity of virulence-associated genes, among which the heterogeneity of VacA and CagA exerts the most prominent impact. As critical elements influencing bacterial genetic variation and adaptive evolution, bacteriophages and genomic islands play pivotal roles in the virulence expression and antimicrobial resistance development of Hp. This article systematically reviews the characteristics and functions of Hp bacteriophages and genomic islands, as well as their roles in host pathogenicity and drug resistance evolution, aiming to provide theoretical references and research insights for the diagnosis, treatment, and development of novel intervention strategies for Hp infection.