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Background: <i>Helicobacter pylori</i> (<i>H. pylori</i>) is significantly linked to various diseases that seriously impact human health, such as gastric ulcers, chronic gastritis and gastric adenocarcinoma. Methods: The compositional shifts in bacterial communities of the orointestinal axis were surveyed pre/post-eradication of <i>H. pylori</i>. In total, 60 samples, including stool and salivary specimens, were collected from 15 <i>H. pylori</i>-positive individuals (HPP) before beginning and 2 months after receiving the eradication therapy. The V3-V4 regions of the 16S rRNA gene were sequenced using MiSeq. Results: Overall, oral microbiomes were collectively more diverse than the gut microbiomes (Kruskal–Wallis; <i>p</i> = 3.69 × 10⁻⁵). Notably, the eradication of <i>H. pylori</i> was associated with a significant reduction in the bacterial diversity along the orointestinal axis (Wilcoxon rank sum test; <i>p</i> = 6.38 × 10⁻³). Interestingly, the oral microbiome of HPP showed a positive correlation between <i>Proteobacteria</i> and <i>Fusobacteria,</i> in addition to a significant predominance of <i>Streptococcus</i>, in addition to <i>Eubacterium_eligens, Haemophilus, Ruminococcaceae, Actinomyces</i> and <i>Staphylococcus</i>. On the other hand, <i>Fusobacterium, Veillonella, Catenibacterium, Neisseria and Prevotella</i> were significantly enriched upon eradication <i>of H. pylori</i>. Generally, <i>Bacteroidetes</i> and <i>Fusobacteria</i> positively coexisted during <i>H. pylori</i> infection along the orointestinal axis (<i>r</i> = 0.67; <i>p</i> = 0.0006). The eradication of <i>H. pylori</i> was positively linked to two distinctive orotypes (O3 and O4). Orotype O4 was characterized by a robust abundance of <i>Veillonella</i> and <i>Fusobacteria</i>. The gut microbiomes during <i>H. pylori</i> infection showed a remarkable predominance of <i>Clostridium_sensu_stricto_1 and Escherichia_Shigella</i>. Likewise, <i>Bifidobacterium</i> and <i>Faecalibacterium</i> were significantly enriched upon eradication of <i>H. pylori</i>. Conclusions: Finally, the impact of eradication therapy clearly existed on the representation of certain genera, especially in the oral microbiome, which requires particular concern in order to counteract and limit their subsequent threats.