Objective To explore the mechanism of Buyang Huanwu Decoction (BYHWD) in alleviating cerebral ischemia reperfusion injury by enhancing the expression of GPX4 and inhibiting iron death. Methods Fourty-eight healthy male SD rats were randomly divided into 4 groups: sham operation group (Sham), model group (MCAO/R), Buyang Huanwu decoction group (BYHWD), and positive control drug group (deferoxamine mesylate, DFO). All experimental animals were established MCAO/R model (sham operation group only stripped). Buyang Huanwu Decoction group (BYHWD) was given Buyang Huanwu Decoction by gavage, DFO group was given DFO by intraperitoneal injection, and other groups were given normal saline by gavage. The indexes were evaluated and materials were taken after 72 hours of reperfusion. Nerve function score was used to detect nerve function; the area of cerebral infarction was measured by TTC staining; Nessler's staining was used to observe the morphological structure of brain tissue; serum GSH, malondialdehyde (MDA) and iron content in brain tissue were detected with biochemical reagents; immunofluorescence and Western blot were used to detect the protein expression of glutathione peroxidase 4 (GPX4). Results Compared with the sham-operated group, the rats in the model group had obvious neurological damage, increased cerebral infarction volume, obvious brain histopathological damage, decreased the number of nissl bodies, increased brain iron content and serum MDA content, and significantly decreased serum GSH content and GPX4 protein expression in brain tissue (P<0.05); compared with the model group, the nerve function of the rats in the Buyang Huanwu Decoction group was significantly improved, the volume of cerebral infarction was reduced, the pathological damage of brain tissue was reduced, the content of iron in brain tissue and serum MDA were decreased, and the content of serum GSH and the protein expression of GPX4 in brain tissue were significantly increased (P<0.05). Conclusion Buyang Huanwu Decoction can inhibit cerebral ischemia reperfusion injury by increasing the expression of GPX4 and inhibiting ferroptosis.