Platelets play a dual role in maintaining and disrupting the blood-brain barrier (BBB) during brain pathology. While traditionally viewed as essential for hemostasis by forming clots to protect the BBB, recent evidence shows that platelets can also damage the BBB by increasing vascular permeability. Platelet-derived factors such as platelet-activating factor (PAF), P-selectin, ADP, and PDGF superfamily proteins (including PDGF-AA, PDGF-CC, and PDGF-BB) contribute to BBB disruption. These factors can induce BBB permeability, trigger neuroinflammation, and promote the release of reactive oxygen species (ROS), which damage endothelial cells. Platelets can also secrete amyloid-beta (Aβ), which further compromises BBB integrity by downregulating tight junction molecules like claudin-5. However, some platelet-derived factors, such as PDGF-BB, may protect the BBB. Platelets can form aggregates with neutrophils, releasing ROS and inflammatory factors that damage the BBB. Additionally, platelets participate in neuroinflammation, which affects BBB integrity. The role of platelets in BBB dysfunction is complex, with some factors promoting BBB damage and others protecting it. Understanding these mechanisms is crucial for developing therapeutic strategies to improve outcomes in brain pathologies such as stroke, Alzheimer's disease, and traumatic brain injury. Further research is needed to clarify the precise mechanisms by which platelets influence BBB integrity and to explore potential therapeutic targets.Platelets play a dual role in maintaining and disrupting the blood-brain barrier (BBB) during brain pathology. While traditionally viewed as essential for hemostasis by forming clots to protect the BBB, recent evidence shows that platelets can also damage the BBB by increasing vascular permeability. Platelet-derived factors such as platelet-activating factor (PAF), P-selectin, ADP, and PDGF superfamily proteins (including PDGF-AA, PDGF-CC, and PDGF-BB) contribute to BBB disruption. These factors can induce BBB permeability, trigger neuroinflammation, and promote the release of reactive oxygen species (ROS), which damage endothelial cells. Platelets can also secrete amyloid-beta (Aβ), which further compromises BBB integrity by downregulating tight junction molecules like claudin-5. However, some platelet-derived factors, such as PDGF-BB, may protect the BBB. Platelets can form aggregates with neutrophils, releasing ROS and inflammatory factors that damage the BBB. Additionally, platelets participate in neuroinflammation, which affects BBB integrity. The role of platelets in BBB dysfunction is complex, with some factors promoting BBB damage and others protecting it. Understanding these mechanisms is crucial for developing therapeutic strategies to improve outcomes in brain pathologies such as stroke, Alzheimer's disease, and traumatic brain injury. Further research is needed to clarify the precise mechanisms by which platelets influence BBB integrity and to explore potential therapeutic targets.