Abstract <p>This article details the synthesis of new <i>N</i>-acylated derivatives of 5-(3-phenoxyphenyl)-1,3,4-oxadiazol-2-amine with high yields using 5-(3-phenoxyphenyl)-1,3,4-oxadiazol-2-amine refluxed with aliphatic anhydrides. Characterization was performed by ¹H, ¹³C NMR, mass and IR spectral studies. The Lysogeny broth Agar dilution method is used to screen the synthetic derivatives for anti-bacterial efficacy with gram-positive bacteria like <i>S. aureus</i> as well gram-negative <i>E. coli</i>. The fungal activity was determined against <i>C. albicans</i>. <i>N</i>-[5-(3-Phenoxyphenyl)-1,3,4-oxadiazol-2-yl]heptanamide exhibited effective antibacterial activity against <i>S. aureus</i>, while <i>N</i>-[5-(3-phenoxyphenyl)-1,3,4-oxadiazol-2-yl]octanamide demonstrates exceptional antibacterial action against <i>E. coli</i>. Whereas remaining compounds have demonstrated a moderate to low level of antibacterial efficiency against <i>S. aureus</i> and <i>E. coli</i>. Based on the results of anti-fungal studies, it was found the compound <i>N</i>-[5-(3-phenoxyphenyl)-1,3,4-oxadiazol-2-yl]octanamide exhibited exceptional antifungal activity against <i>C. albicans</i>. Docking methods were performed to elucidate the binding affinity against ampicillin-CTX-M-15 (PDB ID: 7U4B) using Auto Dock Vina software. Molecular docking studies demonstrate that all compounds exhibit a higher degree of interaction with target proteins.</p>