<p>Thrombotic diseases pose a serious threat to human life and health. Anticoagulant drugs are used to treat and prevent thrombotic diseases. However, although the anticoagulant drugs currently used in clinical practice are effective, they have limitations such as narrow therapeutic window and high risk of bleeding. Therefore, the development of new safe and effective anticoagulants based on natural products and their structural modifications has become an important research direction to overcome the current treatment bottlenecks in this field. In this paper, “thrombotic diseases”, “anticoagulant-active molecules”, “natural products” and “structural modifications” were used as keywords to search the research data on anticoagulant-active molecules published in the past decade in PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases. The research progress of anticoagulant- active molecules from animals and plants was reviewed, which provide basic data for promoting the development of innovative anticoagulant drugs. In this paper, the classification of thrombotic diseases and the clinical drugs currently used in clinical practice are reviewed. Next, the coagulation mechanism and the fact that an imbalance between coagulation and anticoagulation in vivo can lead to thrombosis are described. Finally, the research reports on anticoagulant active compounds and their structural modifications from plants and animals in the past 10 years are summarized. A total of 68 anticoagulant molecules were identified, which provide an important direction and candidate molecules for the development of new, efficient and low-risk anticoagulant drugs.</p> Graphical abstract <p></p>