Mimicking cellular transport mechanisms to make solid-state smart nanochannels has long been of great interest for their diverse applications, but it poses a critical synthetic challenge. Covalent organic frameworks (COFs) are porous crystalline materials with tailor-made nanochannels and hold great potential for ion and molecule transport. We demonstrate here for the first time that 2D COFs possess the necessary merits to be promising solid-state nanochannels for selective transport of amino acids, which are the basis for life. By imine condensations of a C-3-symmetric trialdehyde and a mixture of diamines with and without divinyl groups, two vinyl-functionalized 2D COFs are crystallized. Both multivariant COFs afford straight 1D mesoporous channels formed by AA or AB stacking of layered hexagonal networks. After postmodification with chiral beta-cyclodextrin (beta-CD) via thiol-ene click reactions, the COFs are further fabricated into free-standing mixed matrix membranes (MMMs) that can selectively transport amino acids, as revealed by monitoring not only transmembrane ionic current signature but also concentration changes of permeated substrates. Specially, in the membrane system, the AA stacked COF exhibits higher chiral recognition capability toward histidine enantiomers than the AB stacked COF because of its uniform open channels decorated with beta-CD. This work highlights the great potential of COF nanochannels as a platform for accumulating functional groups for selective transport of small molecules and even biomolecules in the solid state.