Beyond their role in hemostasis, platelets are proposed as key mediators of several physiological and pathophysiological processes of the liver, such as liver regeneration, toxic or viral acute liver injury, liver fibrosis, and carcinogenesis. The effects of platelets on the liver involve interactions with sinusoidal endothelial cells and the release of platelet-contained molecules following platelet activation. Platelets are the major source of circulating extracellular vesicles, which are suggested to play key roles in platelet interactions with endothelial cells in several clinical disorders. In the present review, we discuss the implications of platelet-derived extracellular vesicles in physiological and pathophysiological processes of the liver.