Integrin αIIbβ3, a transmembrane receptor predominantly expressed on platelets, plays a pivotal role in hemostasis and thrombosis. Structurally, it consists of αIIb and β3 subunits that associate non-covalently to form a heterodimeric complex. In its resting state, integrin αIIbβ3 adopts a bent conformation. Upon platelet activation, agonist-induced intracellular signals trigger conformational changes to an extended and open form, enhancing its affinity for ligands such as fibrinogen, a process known as inside-out signaling. Subsequent ligand engagement initiates outside-in signaling, leading to further platelet activation, shape changes, and thrombus stabilization. Deficiency or dysfunction of integrin αIIbβ3 causes Glanzmann thrombasthenia, a bleeding disorder characterized by impaired platelet aggregation. Conversely, hyperactivity of αIIbβ3 contributes to thrombotic disorders, where excessive platelet aggregation leads to arterial thrombosis. As one of the most abundantly expressed receptors on platelets, αIIbβ3 is also a significant target of autoantibodies or alloantibodies, which can cause immune thrombocytopenia. Therapeutically, αIIbβ3 serves as a key target for antiplatelet agents aimed at preventing thrombotic events. U.S Food and Drug Administration (FDA)-approved inhibitors such as abciximab, eptifibatide, and tirofiban bind to αIIbβ3 and block fibrinogen binding and subsequent platelet aggregation. These agents are selectively utilized in the management of acute coronary syndromes and during percutaneous coronary interventions (PCIs) to mitigate ischemic complications. However, their use is associated with risks, including thrombocytopenia and increased bleeding. A comprehensive understanding of the structural dynamics and signaling mechanisms of αIIbβ3 in platelets is essential for the development of more precise and safer therapeutic strategies for managing thrombotic disorders.