To overcome the poor solubility of anticoagulant nano-rare earth (RE) oxides and warfarin/ferulic acid in water, two series of water-soluble anticoagulant materials, RE₂O₃-TDI-PEG-warfarin and RE₂O₃-TDI-PEG-ferulic acid (TDI = toluene 2,4-diisocyanate, RE = La, Eu, Nd, Sc, Sm, Dy), were prepared via a grafting method. The novel materials were characterized by IR, TG, XRD, SEM, TEM, ¹H and ¹³C NRM and particle size tests. The results confirmed that warfarin and ferulic acid were successfully modified onto the surfaces of the rare earth nano-oxides. The anticoagulant properties were evaluated on the basis of coagulation time (CT), recalcification time (RT), activated partial thromboplastin time (APTT) and prothrombin time (PT). It was demonstrated that the novel hybrid materials have better cell compatibility and anticoagulant action than that of warfarin sodium or ferulic acid, due to the increased solubility (>10 mg mL⁻¹) in water and synergy between nano-RE₂O₃ and warfarin/ferulic acid. It was also found that the anticoagulant time of the hybrid materials depends on the concentration i.e., the higher the concentration of hybrid materials, the longer the anticoagulant time. Additionally, Sc₂O₃-TDI-PEG-warfarin and Sc₂O₃-TDI-PEG-ferulic acid exhibited the best anticoagulant properties, which indicate potential application in the medicinal area. These results also provide the opportunity for the development of anticoagulant complexes and the potential for application in other related fields.