Thrombosis is a potentially fatal condition for which various anticoagulant therapies have been used for prevention and treatment. However, bleeding events remain a concern with all anticoagulant drugs. Recent evidence suggests that inhibiting coagulation factor XI (FXI) and activated FXI (FXIa) plays a greater role in the formation of pathological thrombi in thrombosis than in normal hemostatic thrombi, allowing for the potential to address these two events separately. Consequently, FXI/XIa inhibition has become the focus of anticoagulant drug research, leading to the development of numerous FXI-targeting compounds with diverse mechanisms of action. Herein, we aimed to review FXI/FXIa inhibitors under development, discussing the role of FXI in the coagulation reaction and the advantages and disadvantages associated with its deficiency. The results of a Phase II study showed that FXI/XIa inhibitors provide efficacy comparable to that of low molecular weight heparin therapy while reducing clinically significant bleeding events. Additionally, in a study of patients with atrial fibrillation, FXI/XIa inhibitors reduced bleeding events compared to those with direct oral anticoagulants. Furthermore, when combined with antiplatelet therapy, FXI/XIa inhibitors did not significantly increase bleeding risk in non-cardioembolic stroke or acute coronary syndrome. However, conflicting trial results have also been reported, highlighting the difficulty in assessing the clinical benefit of FXI/XIa inhibitors in different clinical settings, such as atrial fibrillation and acute myocardial infarction. Future large, well-designed Phase III studies are needed to evaluate the safety and efficacy of FXI/XIa inhibitors across diverse populations requiring antithrombotic therapy.