ETHNOPHARMACOLOGICAL RELEVANCE: Qizhu Jianwei decoction (QZJWD) is a conventional Chinese medicine formulation used to treat gastric cancer, however, its association with GC and ferroptosis remains poorly understood. AIM OF STUDY: Our research endeavors centered around investigating the potential molecular mechanism of QZJWD in suppressing GC. MATERIALS AND METHODS: A UHPLC-QTOF-MS technique was utilized for determining the major constituents of QZJWD. Laboratory-based experiments such as CCK8, wound healing, transwell invasion assay, and WB were conducted to examine QZJWD's role in influencing HGC-27 and AGS cells, Fe RESULTS: QZJWD treatment markedly suppressed the proliferation, migration, and invasion of gastric cancer cells. QZJWD effectively promoted ferroptosis both in vitro and in vivo, by elevating levels of Fe CONCLUSIONS: QZJWD may induce ferroptosis through the exosome-mediated miR-199-3p/ACSL4 signaling pathway in gastric cancer. Our research identifies a promising approach for addressing GC in clinical settings.