This review discusses the potential of selenium nanoparticles (SeNPs) in protecting the brain from stroke. Strokes are a leading cause of mortality and disability worldwide, and current treatments have significant limitations, particularly the need for high doses of drugs due to the blood-brain barrier (BBB). Nanotechnology offers promising solutions, but most research focuses on anticancer and antiviral effects rather than neuroprotective mechanisms. The review highlights the key molecular mechanisms of brain cell damage during ischemia and examines various nanomaterials, with a particular emphasis on SeNPs. Selenium is a vital microelement that plays a crucial role in neuroprotection through selenoproteins and selenium-containing proteins. SeNPs have been shown to enhance antioxidant status, suppress oxidative stress, and protect brain cells from apoptosis and necrosis. The review also explores the acute and chronic effects of SeNPs, including their ability to activate Ca²⁺ signaling systems, enhance astrocyte function, and modulate gene expression. The protective mechanisms of SeNPs are discussed, along with their potential for stroke prevention and treatment. Despite the promising results, more research is needed to fully understand the mechanisms and optimize the use of SeNPs in clinical settings.This review discusses the potential of selenium nanoparticles (SeNPs) in protecting the brain from stroke. Strokes are a leading cause of mortality and disability worldwide, and current treatments have significant limitations, particularly the need for high doses of drugs due to the blood-brain barrier (BBB). Nanotechnology offers promising solutions, but most research focuses on anticancer and antiviral effects rather than neuroprotective mechanisms. The review highlights the key molecular mechanisms of brain cell damage during ischemia and examines various nanomaterials, with a particular emphasis on SeNPs. Selenium is a vital microelement that plays a crucial role in neuroprotection through selenoproteins and selenium-containing proteins. SeNPs have been shown to enhance antioxidant status, suppress oxidative stress, and protect brain cells from apoptosis and necrosis. The review also explores the acute and chronic effects of SeNPs, including their ability to activate Ca²⁺ signaling systems, enhance astrocyte function, and modulate gene expression. The protective mechanisms of SeNPs are discussed, along with their potential for stroke prevention and treatment. Despite the promising results, more research is needed to fully understand the mechanisms and optimize the use of SeNPs in clinical settings.