Computational outcomes of two isoflavones are carried out through Density Functional Theory (DFT) utilizing the Becke’s 3 and Lee–Yang–Parr (B3LYP) hybrid functional with 6-311G** basis set. All the gas and solvent phase calculations are reported at 298 K and IEF-PCM (Integral Equation Formalism—Polarizable Continuum Model) computations. All the neutral and radical species were stabilized more with reference to total energy in polar medium and less in non-polar medium. The order of stability of both the studied compounds and its radicals are Water > DMSO > Ethanol > Benzene > Gas. The studied isoflavones stabilized more in polar solvents than non-polar solvents by hydrogen bonding and interaction between dipoles. Thus, the computed results proved that 4′-OH sites of both the compounds in B ring possesses best antioxidant efficacy. From the computed results, daidzein isoflavone possesses higher antioxidant capacity than that of genistein with a drop in bond dissociation enthalpy (BDE) value by 2.03 kJ/mol. Lower spin density correlates with lower BDE values and hence confirmed the antioxidant activity. The antioxidant activity of target compounds have also been witnessed by DFT-based reactivity descriptors such as highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), ionization potential (IP), electron affinity (EA) hardness, electrophilicity and Fukui Index.