Abstract <p>In this study, two novel α-aminophosphonic acids (HAP1 and HAP2) derived from 3-aminopropanol and 4-aminobutanol, respectively, were synthesized <i>via</i> modified Irani-Moedritzer reaction, under microwave conditions. It was found that the synthesis method gave a higher yield (in excellent yields (&gt;90%) within very short reaction times (&lt;10 min) in comparison with conventional method. The structures of the obtained molecules were confirmed by different physicochemical methods (FT-IR, ¹H-NMR, ³¹P-NMR and Elemental Analysis). In order to know the effect of the main side chain length and the phosphonomethyl moiety addition on the structures, electronic, vibrational and thermodynamic proprieties, the Density Functional Theory (DFT) at the B3LYP/6–31G(<i>d</i>, <i>p</i>) level was used. Moreover, a comparative study between the obtained molecules (HAP1) and (HAP2) has been made to determine different properties of these products and analyzed by means of the HOMO–LUMO properties. The global reactivity descriptors, Mulliken atomic charges and dipole moment of the two molecules were also calculated and discussed. In addition, the synthesized molecules were screened for their antioxidant potential using: ABTS⁺ and DPPH which exhibited excellent activity, particularly with compound (HAP2) for all the antioxidants assays. Furthermore, the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-negative (<i>E. coli</i> and <i>P. aeruginosa</i>) and two Gram-positive bacterial strains (<i>S. pyogenes</i> and <i>S. aureus</i>) by disk diffusion method. Among synthesized compounds, compound HAP1 showed potent inhibitory activity compared to standard antibiotic. The investigated molecules may be used as lead molecules for designing new therapeutically effective antibacterial and antioxidant agents.</p>