Density functional theory (DFT) methods have been employed in this work to study the adsorption behavior of eugenol (Eug) on the external surface of pure and Si-doped Al12N12 and B12N12 fullerene-like nanocages. All calculations were performed using the M062X-D3 functional combined with the 6-311 + G(d,p) basic sets. In order to probe the reliability of the DFT method, three other functionals (B3LYP-D3, CB3LYP-D3 and WB97XD) were employed and no significant difference was observed in the adsorption energy values of the most stable configurations (AEII and BEII). Also, the complexes are found to be stable in standard conditions in gas and aqueous phases, and the adsorption process is found to be exothermic and spontaneous. Interestingly, Si-doped nanomaterials (Si-AEII and Si-BEII) form the most stable adsorbent-adsorate molecular states (Eads = −90.07 and −61.42 kcal/mol respectively) in gas phase. Furthermore, Si-AEII and Si-BEII complexes exhibit the highest reactivity, characterized by the lowest values of the HOMO-LUMO energy gap (5.50 and 7.07 eV respectively). MEP map of the studied systems showed electron rich and electron deficient sites. Natural bond orbital analyses revealed that the interaction of Al12N12 with Eug is mainly due to the strong electron delocalization LP(2)O10 → LP*(2)Al47 (E(2) = 34 kcal/mol), whereas in Eug-B12N12 complex, it is mainly due to the electron delocalization LP(2)O10 → P*(4)B36 (E(2) = 96.53 kcal/mol). The QTAIM analysis revealed that Si–O and Al–C/B–C bonds linking eugenol to doped cages are attractive weak interactions and their nature have been confirmed via RDG/NCI analyses. Indeed, the present study revealed the suitability of Si-doped Al12N12 and B12N12 fullerene-like nanocages for the efficient drug delivery of eugenol.