Metabolic dysfunction-Associated Steatotic liver disease (MASLD) is one of the most common systemic diseases causing chronic liver diseases. Current evidence indicates that cognitive-related deficits occur frequently in MASLD, causing significant impacts on patients and their families, and even possibly increasing the economic and psychological burdens on healthcare, productivity, and nursing staff. However, there are currently no effective treatment methods. This article reviews the pathogenesis of cognitive dysfunction in MASLD, finding that platelet activation is elevated. Furthermore, recent studies have found that platelets can send and receive signals to the central nervous system (CNS), serving as an important bridge between the brain and peripheral organs. This article reviews changes in platelets associated with MASLD and investigates the role of platelet activation, with the goal of offering novel approaches for diagnosing and treating cognitive dysfunction in MASLD.