Chronic non-healing wounds are one of the most common complications of diabetes mellitus and results in a huge physical and mental burden for patients. Panax notoginseng saponins (PNS) have a wide range of applications in anti-apoptosis, anti-oxidation, and promoting blood circulation. Our study aimed to explore whether PNS could improve diabetic wound healing. High-glucose (HG, 30 Mm) were used to incubated human umbilical vein endothelial cells (HUVECs) to simulate the hyperglycemia environment in vivo, and 200 μg/ml (optimum harmless concentration screened) PNS was added into HG-incubated HUVECs to investigate the protective effect of PNS on the cells. Compared with control, high glucose treatment significantly suppressed HUVEC proliferation, invasion, migration, angiogenesis, malondialdehyde (MDA) production and nitric oxide (NO) release, promoted cell apoptosis, and deactivated the GSK-3β/β-catenin/ VEGF pathway. PNS treatment could largely rescue the effects of HG on cell dysfunction and improve the deactivation of GSK-3β/β-catenin/VEGF pathway. ICG-001, a small molecular β-catenin inhibitor that can selectively antagonize β-catenin mediated transcriptional activity, could eliminate the protective effects of PNS on cell dysfunction and activation of GSK-3β/β-catenin/VEGF pathway. Moreover, Furthermore, a diabetic model (50 mg/kg streptozotocin induced) with back skin wound was established in rats, and the wounds were administrated with petrolatum, gelatin/Bletilla striata gelatin (GT/BSGT), or GT/BSGT plus PNS. We found that PNS signally facilitated wound healing and matrix remodeling in vivo. In conclusion, our study verified that PNS improved wound healing in hyperglycemic rats via promoting endothelial cell proliferation, invasion, migration, angiogenesis, suppressing cell apoptosis and oxidative damage, and activating the GSK-3β/β-catenin pathway.