Hexadimethrine bromide (HB), a polycation to neutralize heparin and control internal bleeding, may also cause serious blood coagulation that may be life-threatening. Reversal of HB by heparin and vice versa might potentially lead to a vicious circle of alternative bleeding and blood coagulation. In this Letter, a biocompatible synthetic nanoreceptor, cucurbit[7]uril (CB[7]), was demonstrated to dramatically alleviate HB-induced blood coagulation in vitro as well as in vivo, through the formation of HB@CB[7] polypseudorotaxanes. This discovery, for the first time, suggests the significant clinical potential of a synthetic receptor in alleviating the side effects and toxicity of a polycationic drug.