Stroke is a serious cerebrovascular disease that can be classified into two types: ischemic and hemorrhagic. It has a high mortality and disability rate, and current methods of prevention and treatment are limited. One promising cytokine that may help in the prevention and treatment of stroke is interleukin-27 (IL-27). IL-27 has been shown to have potent immunoregulatory effects in the brain, including inhibiting T-cell proliferation and promoting the differentiation of regulatory T cells. These effects can help reduce inflammation, inhibit cell death and protect against neurodegeneration. Recent animal studies have shown that IL-27 can reduce neural damage caused by ischemic and hemorrhagic stroke; however, it is still far from clinical application. This review will briefly introduce the epidemiological characteristics of stroke and the role of IL-27 in immunomodulation, describe the neuroprotective effects and related mechanisms of IL-27 in both types of stroke, explain the research advances regarding IL-27 in both types of stroke, introduce brain-targeted delivery strategies for IL-27, provide evidence for the potential clinical value of IL-27, and discuss possible risks and solutions in clinical applications. This study informs the future translational application of IL-27 in the treatment of stroke.