Platelets play a dual role in maintaining the blood-brain barrier (BBB) integrity during brain pathology. While they are traditionally known for their role in thrombosis and hemostasis, recent studies have highlighted their involvement in neuroinflammation and BBB disruption. Activated platelets release various factors that can enhance vascular permeability and damage the BBB. These factors include platelet-activating factors (PAF), P-selectin, adenosine diphosphate (ADP), platelet-derived growth factors (PDGF) superfamily proteins (especially PDGF-AA and PDGF-CC), Amyloid-β (Aβ), and reactive oxygen species (ROS). Platelets can also form platelet-neutrophil aggregates (PNAs) that release ROS and inflammatory factors, further contributing to BBB dysfunction. Conversely, some platelet-derived factors, such as PDGF-BB, protect the BBB. The mechanisms underlying these dual roles of platelets in BBB integrity are complex and require further investigation. Understanding these mechanisms may provide new therapeutic targets for brain diseases characterized by BBB disruption.Platelets play a dual role in maintaining the blood-brain barrier (BBB) integrity during brain pathology. While they are traditionally known for their role in thrombosis and hemostasis, recent studies have highlighted their involvement in neuroinflammation and BBB disruption. Activated platelets release various factors that can enhance vascular permeability and damage the BBB. These factors include platelet-activating factors (PAF), P-selectin, adenosine diphosphate (ADP), platelet-derived growth factors (PDGF) superfamily proteins (especially PDGF-AA and PDGF-CC), Amyloid-β (Aβ), and reactive oxygen species (ROS). Platelets can also form platelet-neutrophil aggregates (PNAs) that release ROS and inflammatory factors, further contributing to BBB dysfunction. Conversely, some platelet-derived factors, such as PDGF-BB, protect the BBB. The mechanisms underlying these dual roles of platelets in BBB integrity are complex and require further investigation. Understanding these mechanisms may provide new therapeutic targets for brain diseases characterized by BBB disruption.