Design and synthesis of novel series of 1,3,4-oxadiazoles containing FQs derivatives and screened their antibacterial, antimycobacterial properties. The synthesized compounds were characterized by different spectral techniques like IR, 1H NMR, 13C NMR, mass and elemental analysis. The results of the antimicrobial activity and compounds 6d, 6b, 6e, 6f and 6a demonstrated potent antibacterial activities with zone of inhibition of 42, 36, 37, 34 and 30mm against S. aureus, E. faecalis, S. pneumoniae, E. coli and K. pneumoniae, respectively. 1,3,4-Oxadiazole derivatives 6a, 6b, 6g were showed excellent antimycobacterial activity against M. smegmatis H37Rv with MICs 22.35, 16.20, 20.28µg/mL, respectively. FQs 6d and 6b exhibited highest hydrogen bonding interactions with Asp83 (3.11 A˚), Ser80 (2.15 A˚) Asp27 (σ-σ), Arg87 (Π-Π), Arg87 (Π-Π), Ser80 (σ-σ), Ala84 (σ-σ) and binding energies ΔG = - 6.41, - 6.97kcal/mol with active site of topoisomerase-IV from S. pneumoniae [4KPE]. We performed a computational investigation of compounds 6a-j for their absorption, distribution, metabolism and excretion (ADME) properties by using the Molinspiration, Molsoft toolkits. The ligands 6f, 6d and 6b reveal the highest pharmacokinetic properties and possess maximum drug-likeness model score 1.59, 1.46 and 1.23, respectively.