Oxytocin, a hormone best known for social bonding, also protects brain cells during a stroke. It helps keep the blood‑brain barrier intact, calms inflammation, reduces oxidative damage, and supports brain‑blood vessel repair. The biggest hurdles are getting enough oxytocin into the brain and figuring out the right timing and dose for each person.

Ischemic stroke (IS), also known as ischemic cerebrovascular accident, is a serious consequence of cerebral ischemia characterized by high morbidity, disability, and mortality. The primary causes of IS include atherosclerosis, cardiogenic embolism, large artery occlusion, and small artery disease. The occurrence of IS involves multiple cellular death mechanisms such as vascular obstruction, inflammatory response, excitotoxicity, oxidative stress, as well as neuronal apoptosis, necroptosis, and pyroptosis. Despite the application of current drugs and therapeutic strategies in the treatment of IS, their efficacy remains limited, and they are often accompanied by adverse effects. Therefore, identifying novel and more effective treatment strategies is of critical importance. In recent years, oxytocin (OT) has attracted widespread attention due to its multiple biological effects in the central nervous system, especially its neuroprotective effects. OT can reduce ischemic damage by stabilizing the blood-brain barrier (BBB), inhibiting neuroinflammation, alleviating oxidative stress, regulating excitotoxicity, and calcium overload. Additionally, OT promotes neurovascular remodeling via the VEGF/BDNF axis and modulates Na⁺/K⁺-ATPase activity, GABA signaling pathways, and DNA methylation, thereby contributing to recovery after stroke. However, the pharmacokinetic characteristics of OT, limitations in delivery methods, and the challenges of individualized treatment restrict its clinical application. This review will summarize the mechanisms of OT in IS, discuss the challenges and limitations in its clinical application, and explore future development directions, including optimization of nasal delivery systems, development of nanodrug carriers, use of perfusion-weighted imaging to determine the therapeutic window, and personalized treatment strategies based on genetic profiling. The aim is to provide theoretical support and guidance for further research on OT and its clinical application.