A series of 1-(2, 4-dimethoxy-5-[3-(substituted-phenyl)acryloyl]phenyl)-4-(substituted-phenyl)but-2-en-1-ones (3a-e) were synthesized and evaluated for their antimicrobial actions. Resorcinol was used as starting material for the preparation of 1, 1´-(4, 6-dihydroxy-1, 3-phenylene) diethanone (1), which then treated with dimethylsulphate to obtain 1-(5-acetyl-2, 4-dimethoxyphenyl)-1-ethanone (2). Compound (2) was reacted with substituted aromatic aldehydes in ethanol in presence of KOH to furnish the title compounds (3a-e). The structures of the synthesized compounds were confirmed on the basis of  1H-NMR, Mass and elemental analysis results. The antimicrobial activity (minimum inhibitory concentration; MIC) of the title compounds was determined against some selected bacterial and fungal strains. Two compounds, 3d and 3e, showed good antimicrobial activity against S. aureus and E. coli.