Objective To review the current clinical application status and research progress of different anticoagulants in the perioperative period of free flap transplantation. Methods A comprehensive review of recent relevant literature was conducted, focusing on clinical research concerning the application of anticoagulants in the perioperative period of free flaps. The administration regimens, timing, dosage selection, effectiveness, and safety of commonly used and novel anticoagulants were summarized. Results At present, the anticoagulants mainly used in the perioperative period of free flap transplantation include antivenous thrombotic drugs, antiarterial thrombotic drugs, and physical/colloidal anticoagulants, etc. Anticoagulation regimens can be classified into two major categories: single-agent anticoagulation and combined anticoagulation. Single-agent anticoagulation mainly includes unfractionated heparin, low-molecular-weight heparin, aspirin, and new anticoagulation drug regimens. Combined anticoagulation is commonly a synergistic anticoagulation regimen dominated by heparin drugs, combined with aspirin, different antiplatelet drugs, and expansion agents. Studies indicate that perioperative anticoagulant administration can effectively reduce the risk of thrombosis in free flaps and improve the overall flap survival rate. However, significant differences exist in the impact of drug types, administration routes, initiation timing, and dosage intensity on efficacy and bleeding risk. A unified, standardized application protocol has not yet been established. In addition, there has been a growing number of studies on novel anticoagulant drugs. However, their superiority and optimal application strategies in the field of free flap transplantation still necessitate more high-quality evidence. Conclusion Perioperative anticoagulation therapy is one of the key strategies to improve the survival rate of free flaps, but there is still a lack of advanced evidence-based evidence to establish a standard protocol at present. Future research should focus on the optimization of individualized anticoagulation strategies, the validation of the effectiveness of new anticoagulants, and the exploration of the advantages of different anticoagulation regimens. At the same time, attention should be paid to balancing anticoagulation and bleeding risks to promote the standardization of clinical practice and the improvement of treatment safety.