To investigate the impact of Qiwei Baizhu Powder on the Wnt/β-catenin signaling pathway in the hippocampus of DCI(diabetic cognitive impairment) rat model established through prolonged high-fat diet feeding combined with 1% streptozotocin administration. Following successful establishment of the DCI model, five groups were designated: DZ(control) group, MX(model) group, QWBZ (Qiwei Baizhu powder) group, and a combination Western medicine group (metformin and rosiglitazone, LHXY). After each group received the respective treatments of QWBZ (1.6 g/mL) in combination with Western medicine (52 mg/mL) or normal saline for a period of 6 weeks (2 mL per animal), orbital venous blood was collected to measure FPG (fasting plasma glucose) levels. FINS(fasting insulin) levels were determined using ELISA, and ISI (insulin sensitivity index) was subsequently calculated. MWM (Morris water maze) system was utilized to assess the alterations in spatial navigation paths and times of rats subjected to DCI(delayed cerebral ischemia). The morphological changes in rat hippocampal tissue were obtained through HE (hematoxylin and eosin)-stained sections. The mRNA and protein expression levels of PKA (protein kinase A), β-catenin, and GSK-3β (glycogen synthase kinase 3β) were quantified by qPCR (quantitative real-time PCR) and Western blot analysis, respectively. IHC (immunohistochemistry) was employed to investigate the expression and distribution of phosphorylated GSK-3β protein. The results show that Qiwei Baizhu Powder can effectively reduce the FPG value of DCI rats (P<0.01), regulate ISI index (P<0.01), and improve the morphological destruction of nerve cells in hippocampus. Compared with MX group, Qiwei Baizhu Powder could significantly reduce the expression of APC and GSK-3β mRNA and protein in hippocampus of rats (P<0.01), increase the expression of β-catenin (P<0.01), and increase the relative expression of P-GSK-3β protein (P<0.01), so as to alleviate the damage of hippocampal neurons. Qiwei Baizhu Powder may play a role in the intervention of cognitive dysfunction complicated by diabetes mellitus by regulating Wnt/β-catenin signaling pathway.