The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.