The effects of substituents on the structure, character, and nonlinear optical (NLO) properties of the organic alkalide Li+(calixpyrrole)Li− were studied by density functional theory. Natural bond orbital analysis and vertical ionization energies reveal that electron-donating substituents strengthen the alkalide character of Li+(calixpyrrole)Li− and that they are beneficial for a larger first hyperpolarizability (β0) value. However, electron-withdrawing substituents have the opposite effect. The dependence of the NLO properties on the number of substituents and their relative position was detected in multisubstituted Li+(calixpyrrole)Li− compounds. For both the amino- and methyl-substituted derivatives, the polarizabilities and the first hyperpolarizabilities increase as more pyrrole β-H atoms are substituted. Moreover, distribution of the substituents so that they are as far away from each other as possible resulted in an increase in the β0 value. The new knowledge obtained in this study may provide an effective approach to enhance the NLO responses of alkalides by employing pyrrole derivatives as complexants.