Homochiral metal-organic frameworks with fine-tuned pore sizes/walls and large surface areas are promising porous materials for enantioseparation considering the traditional zeolite molecular sieves have no chirality. Using enantiopure pyridyl-functionalized salen [(N-(4-Pyridylmethyl)-L-leucine·HBr)] as a starting material, we have prepared a noninterpenetrated three-dimensional homochiral metal organic framework {[ZnLBr]·H2O}n, which was further used as a chiral stationary phase for high-performance liquid chromatography to enantioseparate racemic drugs, showing excellent performances in enantioseparation of drugs. The metal-organic framework can be regarded as a novel molecular sieve-like material with a chiral separation function based on the relative sizes of the chiral channels and the resolved molecules.