Using a convergent synthetic method, a series of nicotine derivatives were synthesized from the basic materials nicotine-N-oxide in good yields. The structures of the synthesized compounds were confirmed by spectral methods of analysis (FT-IR, 1H-NMR, and 13C-NMR). Most of the target compounds were tested for antibacterial activity against five kinds of bacteria; the tested compounds exhibited varying levels of activity against both gram-negative and gram-positive bacteria. The results of bioactivities showed that some of the target compounds exhibited good antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes, and Klebsiella pneumoniae. In addition, the broad spectrum anti-microbial action of nicotine derivatives developed in the present study may find immense applications in formulating new disinfection or decontamination strategies against widely spreading pathogens of clinical significance.