In the present work, the synthesis and antimicrobial activity of new thiazolyl substituted 1,3,4-oxadiazole derivatives were achieved. The reaction of different thioamides with ethyl 4-chloro-3-oxobutanoate (4-chloroethyl acetoacetate) gave derivatives of ethyl 2(2-arylthiazol-4yl)acetate, which on subsequent reaction with hydrazine hydrate in absolute ethanol afforded 2-(2-arylthiazol-4-yl)acetohydrazide derivatives. The obtained 2-(2-arylthiazol-4-yl)acetohydrazide derivatives on reaction with CS₂ and KOH in aqueous ethanol cyclized to form 5-((2-arylthiazol-4-yl)methyl)-1,3,4-oxadiazole-2-thiol derivatives. Finally, the obtained 1,3,4-oxadiazoles were further treated with α-halo ketones at room temperature to afford the targeted thiazolyl oxadiazole derivatives. Most of the compounds showed good antibacterial as well as antifungal activity.