Thrombus is one of the major threats to human health. The prevalence of thrombosis-induced cardio-cerebrovascular diseases is increasing worldwide. According to the mechanism of thrombosis, antithrombotic drugs are divided into three categories. These categories are anticoagulants, platelet inhibitors, and fibrinolytics. Today, a large number of substances with antithrombotic activity are emerging. They aim to eliminate the unavoidable drawbacks of previously approved drugs. Such drawbacks include a high risk of bleeding and slow onset of action. Unlike drugs, food-derived functional substances are often considered to have no (or low) side effects. They are also more readily absorbed and utilized by the body. This chapter firstly describes the causes and mechanisms of thrombosis. It also provides an overview of the antithrombotic activity of bioactive peptides from marine shellfish. The screening, identification, and bioactive labeling of such bioactive peptides are also summarized. Biochemical methods, cellular models, and animal models are related to the determination of antithrombotic activity. They are also described in this chapter. In conclusion, the marine shellfish protein peptides presented in this chapter provide some new ideas. These ideas are for the prevention of thrombotic diseases. They also contribute to practical applications in the food industry.