Diabetes can pathologically alter blood vessels in various locations and can lead to strokes if brain vessels are directly affected. In addition, mortality rates are higher and post-stroke outcomes are worse in stroke patients with uncontrolled glucose levels. Treatment options for ischemic stroke are limited, and the development of new therapeutic agents or combination therapies is essential. Growing evidence suggests that metformin treatment, due to its anti-inflammatory action, exerts a neuroprotective effect against brain damage from ischemia/reperfusion. Metformin is a biguanide drug that is widely used for its safety and low cost, especially for the treatment of diabetes. In clinical population, chronic metformin treatment is associated with a lower risk of stroke and reduced cardiovascular mortality.