<p>Ischemic stroke rate is increasing globally and causing a burden on society. The FDA- approved treatments (tissue plasminogen activator and mechanical thrombectomy) come with a series of limitations, such as a narrow therapeutic time window and failure to restore the dying neurons. The area around the ischemic core, known as the penumbra, can be saved and the number of dying neurons could be reduced. This goal can be achieved through reducing inflammation, oxidative stress, and cell apoptosis, All which result as secondary damage following cerebral ischemia. Therefore, identifying new pharmacological agents that possess neuroprotection are of significant interest. Piperine is an alkaloid from the <i>Piperaceae</i> family and has shown benefits for various neurological diseases including Alzheimer’s, Parkinson and epilepsy. Piperine has shown to inhibit inflammation, apoptosis, and oxidative stress, all of which contribute to worse stroke outcomes. Piperine’s impact on blood pressure is also noteworthy since controlling blood pressure, both before and after stroke management, is necessary. Few pre-clinical studies have demonstrated that piperine holds the potential to alleviate stroke severity. While the precise mechanism remains unclear, studies indicate that these beneficial effects are due to its immunomodulatory and neuroprotective mechanisms. Piperine has also been shown to enhance the bioavailability of various pharmacological agents and it could be used in combination with other neuroprotective agents to yield optimum results in stroke management. Despite the promising evidence, utilizing piperine in the stroke setting has not yet been established and future studies are required to shed light on its effects on stroke. This review explores the mechanisms by which piperine may impact stroke, highlighting its underlying mechanisms as supported by existing literature and laboratory findings.</p> Graphical Abstract <p>Therapeutic effects of piperine in Ischemic stroke</p> <p></p>