Helicobacter pylori is a gram-negative carcinogenic intestinal pathogen that infects about 50% of humans worldwide. The impact of H. pylori eradication therapy on the oral and gut microbiota of teenagers is yet unknown. Thus, this study evaluated alterations in the oral and gut microbiome after triple therapy eradication in teenagers. A total of 20 salivary and 20 fecal samples were collected pre and 8 weeks post eradication therapy. The orointestinal microbiota axis was analyzed with 16S rRNA next-generation sequencing of the V3-V4 hypervariable region. The composition and diversity of oral and gut microbiota were compared before and after H. pylori eradication therapy. For oral samples, there was a decrease in the abundance of the families Streptococcaceae, Saccharimonadaceae, Actinomycetaceae, Fusobacteriaceae, Lachnospiraceae, Staphylococcaceae and Micrococcaceae after eradication treatment versus an increase in the relative abundance of Prevotellaceae, Neisseriaceae, Veillonellaceae, Leptotrichiaceae, Pasteurellaceae, Porphyromonadaceae, Family_XI and Carnobacteriaceae. For stool samples, the relative abundance of Clostridiaceae_1, Peptostreptococcaceae, Coriobacteriaceae, Streptococcaceae, Pseudomonadaceae, Enterobacteriaceae, Eggerthellaceae, Prevotellaceae decreased after eradication treatment, whereas the relative abundance of Ruminococcaceae, Lachnospiraceae, Bifidobacteriaceae, Bacteroidaceae, Methanobacteriaceae, Veillonellaceae, and Erysipelotrichaceae increased. There was significant difference in alpha diversity of oral and fecal samples pre and post eradication treatment. Triple therapy reduced the microbial diversity after eradication treatment in both oral and fecal samples.