A new series of 2-(substituted phenyl)-5-(5-chloro quinolin-8-yloxy) methyl-1,3,4-oxadiazole (3a-j) were synthesised after refluxing 2-[(5-chloro quinolin-8-yl) oxy] acetohydrazide (2) with different aromatic acids in presence of POCl3. A new series of N'-(substituted benzylidene)-2-(5-chloro-8-yloxy) acetohydrazide (schiff’ bases) (4a-j)were also synthesized from a mixture of2-[(5-chloro quinolin-8-yl) oxy] acetohydrazide (2)and different aromatic aldehydes in presence of glacial acetic acid. The chemical structures of these compounds were confirmed by various physic-chemical methods viz, IR, 1HNMR, mass spectral data and elemental analysis. Newly synthesized compounds were screened in vitro for their antimicrobial activity against varieties of gram +ve and gram -ve bacterial strains such as Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and fungi strains Candida albicans & Aspergillus nigar with MIC at 40 μg/mL. The newly synthesized Schiff bases and 1,3,4- Oxadiazole derivatives bearing 5-chloroquinolin-8-ol are showing moderate to highly significant antimicrobial activity. The Schiff base (4i) shows highly significant antimicrobial activity as compare to other synthesized Schiff bases.