Enantiomers have the same physical properties but different chemical properties due to the difference in the orientation of groups in space and thus Chiral discrimination is quite necessary, as an enantiomer of drug can have lethal effects. In this study, we used the CC2 cage for chiral discrimination of amino acids using density functional theory. The results indicated the physisorption of amino acids in the central cavity of the cage. Among the four selected amino acids, proline showed maximum interactions with the cage and maximum chiral discrimination energy is also observed in the case of proline that is 2.78 kcal/mol. Quantum theory of atoms in molecules and noncovalent interaction index analyses showed that the S enantiomer in each case has maximum interactions. The charge transfer between the analyte and surface is further studied through natural bond orbital analysis. It showed sensitivity of cage for both enantiomers, but a more pronounced effect is seen for S enantiomers. In frontier molecular orbital analysis, the least EH-L gap is observed in the case of R proline with a maximum charge transfer of −0.24 e-. Electron density difference analysis is carried out to analyze the pattern of the charge distribution. The partial density of state analysis is computed to understand the contribution of each enantiomer in overall density of the complexes. Our results show that S-CC2 porous organic cages have a good ability to differentiate between two enantiomers. S-CC2 porous organic cages efficiently differentiated the S enantiomer from the R enantiomers of selected amino acids.