In clinical practice, antiplatelet, anticoagulant and fibrinolytic drugs are the mainstay of thrombosis treatment, but their potential bleeding side effects limit their widespread use. Therefore, modifying these existing drugs or developing new therapies that mitigate bleeding risks while maintaining their efficacy and utilization is necessary. Since the critical role of platelets in thrombosis is closely related to their cell surface receptors, intracellular signaling pathways and metabolism, current research focuses on these three major classes of platelet targets to develop new antithrombotic drugs. The coagulation cascade has always been the main target of anticoagulant drugs, but since the role of molecules of the contact system is more critical in thrombosis than in hemostasis, molecules targeting the contact system, such as FXIa and FXIIa, have become the main direction of anticoagulant drug research at present. Moreover, since the inflammatory response has been found to be significantly associated with thrombosis in recent years, the development of drugs that target inflammatory pathways, such as inflammasome, has also become a hot topic. This article provides a detailed description of these targets or drug formulations that are currently being investigated, including their mode of action and antithrombotic efficiency, and also points out their existing shortcomings. Moreover, antithrombotic nanomedicines can achieve precise release of drugs, which can greatly improve the thrombolytic efficiency and reduce side effects. In conclusion, this review focuses on summarizing the current new targets and new methods of antithrombotic drug research, hoping to provide a little reference for future related research.