Chiral organic compounds are the excellent second-order nonlinear optical (NLO) materials due to their intrinsic non-symmetric structures and combined with the merits of organic compounds. Here, the ground electron structures, excited-state electron transition, and second-order NLO property of novel chiral covalent organic cages (COCs) (Solomek et al., 2017) consisting of naphthalene-1,4:5,8-bis(dicarboximide) (NDI) units, have been fully investigated by DFT/TDDFT. The simulated electron absorption wavelengths are in good agreement with experimental ones, allowing us to assign their electron transition characters with high confidence. Based on the experimental structures, we designed eight compounds to probe the effect of different substitutions on photophysical properties. It is found that the substitution of NH 2 and NO 2 groups at opposite side of NDI and replacement of cyclohex-1,2-diyl with benzene are the most effective way to not only tune energy gaps and electron transition properties but also enhance the NLO response. For instance, the second-order NLO value of compound 2-h is about 80 times as large as the organic urea molecule. Our work is also important for fully understanding photophysical properties and extending potential applications of chiral COCs.