The molecular interaction between an extrinsic fluorescence probe (EFP) and dissolved organic matter (DOM) was calculated using the density functional theory (DFT) at the B3LYP/LANL2DZ level. Eight different types of DOM were selected from the compositions often found in food and beverages. EFP models were obtained from Cambridge Crystallographic Data Centre (CCDC). To avoid problems, all metalloporphyrins and their complexes were optimized at three different spin states. Relative energies indicated that the calculated models possessed the most stable structures at doublet states, except for ZnP–O2. The binding ability representing the sensitivity of the EFP to specific DOM was analyzed using the binding energy. The binding energies were classified into two sensitivity groups with relatively high sensitivity to the binding of O2, H2S, and L2,4,5, whereas N2 and L1,3 could not easily be detected by a ZnP probe. Our theoretical results may be useful for the design of EFPs.