The interactions between chemosensors, 3-amino-5-(4,5,6,7-tetrahydro-1H-indol-2-yl)isoxazole-4-carboxamide (AIC) derivatives, and different anions (F- Cl-, Br-, AcO-, and H2PO4-) have been theoretically investigated using DFT approaches. It turned out that the unique selectivity of AIC derivatives for F- is ascribed to their ability of deprotonating the host sensors. Frontier molecular orbital (FMO) analyses have shown that the vertical electronic transitions of absorption and emission for the sensing signals are characterized as intramolecular charge transfer (ICT). The study of substituent effects suggests that all the substituted derivatives are expected to be promising candidates for fluoride chemosensors both in UV-vis and fluorescence spectra except for derivative with benzo[d] thieno[3,2-b]thiophene fragment that can serve as ratiometric fluorescent fluoride chemosensor only.