Platelets play a critical role in hemostasis at sites of injury and are capable of interacting with various types of cells in the bloodstream. The promise of utilizing platelets for diagnostic and therapeutic applications has motivated the development of facile strategies to functionalize platelets. However, platelets with a small size, lack of nucleus and efficient protein machinery, and low tolerance to chemicals and transfection agents have posed significant challenges for chemical or genetic engineering. Here, for the first time, we report successful metabolic glycan labeling of platelets to introduce chemical tags (e.g., azido groups) onto the membrane of platelets. We demonstrate that azido-sugars can metabolically label platelets in a concentration dependent manner, with cell-surface azido groups detectable at as early as 4 hours. The cell-surface azido groups enable the conjugation of various macromolecular cargos including proteins and polymers onto platelets via efficient click chemistry. Small-molecule drugs such as doxorubicin can also be conjugated onto azido-labeled platelets and become subsequently released to kill surrounding cancer cells, demonstrating the feasibility of utilizing platelets as a drug delivery vehicle. We further show that azido-sugars, upon intraperitoneal injection, can metabolically label platelets with azido groups