In vitro antibacterial activity of the novel piperidone derivatives synthesised from chalcone in dry media under microwave irradiation through the Michael addition reaction has been represented. It's a comparative study of synthesizing compounds by conventional as well as non-conventional methods of specific greener process. Then the structures of newly synthesized compounds were characterized by FT-IR, UV-Vis, NMR ( 13 C, 1 H) and GC-Mass spectrums were investigated. The in vitro antimicrobial activities were screened against the standard strains: Staphylococcus aureus, Streptococcus pyogenes and Bacillus subtilis as Gram positive, Escherichia coli and Pseudomonas aeruginosa as Gram negative. Nitrile group containing piperidone derivative 5d showed better antibacterial activity on Streptococcus pyogenes, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa than the reference drug Ciprofloxacin.