Background <p>This study evaluated the clinical efficacy and safety of acupoint application of traditional Chinese medicine (TCM) combined with Kangyou Decoction in patients with <i>Helicobacter pylori</i> (<i>Hp</i>) infection presenting with damp-heat syndrome obstructing the middle jiao.</p> Methods <p>A total of 416 patients with <i>Hp</i> infection and TCM-defined damp-heat syndrome of the middle jiao were enrolled and randomly assigned to a treatment group (<i>n</i> = 208) or a control group (<i>n</i> = 208). The control group received standard bismuth-containing quadruple therapy, while the treatment group received acupoint application of TCM combined with oral administration of Kangyou Decoction. Both groups underwent treatment for two weeks. Outcomes included Hp eradication rates, changes in TCM syndrome scores pre- and post-treatment, and the incidence of adverse reactions.</p> Results <p>Following two weeks of therapy, no statistically significant difference in <i>Hp</i> eradication rates was observed between the two groups (<i>p</i> &gt; 0.05). Both groups demonstrated significant improvement in TCM syndrome scores (<i>p</i> &lt; 0.05), with the treatment group showing a greater reduction compared to the control group (<i>p</i> &lt; 0.05). The total effective rate in the treatment group was higher than that in the control group. Incidences of adverse reactions did not differ significantly between the groups (<i>p</i> &gt; 0.05).</p> Conclusion <p>Acupoint application combined with Kangyou Decoction yielded comparable Hp eradication outcomes to bismuth quadruple therapy in patients with damp-heat syndrome of the middle jiao. The combined therapy demonstrated greater improvement in clinical symptoms with a favorable safety profile, supporting its potential for clinical application.</p>