Ischemic stroke (IS), as a common cerebrovascular disease, is characterized by high disability, mortality, recurrence, and complications. Studies have shown that Buyang Huanwu Decoction (BHD) can impact the treatment of acute cerebral infarction, subsequent recovery, and sequelae. However, the mechanism of action of BHD in IS treatment remains unclear. To this end, we applied a combined network pharmacology and proteomics approach to investigate the mechanism of action of BHD. First, the chemical components of BHD were revealed by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS/MS). The molecular mechanism of BHD in treating IS was preliminarily elucidated through a network pharmacological approach. Subsequently, proteomic studies were used to explore the biomarkers of BHD in IS treatment