Background: A series of bis(indolyl)methanes (3a-3o) have been synthesized using a greener and new approach using the reaction of different substituted aldehydes and indole in the presence of an easily available and biodegradable base such as piperidine in acetic acid at room temperature and characterized with UV (Ultraviolet-visible spectroscopy), Gas Chromatography-Mass Spectrometry (GCMS), Proton Nuclear Magnetic Resonance (H-NMR), and Fourier Transform Infrared Spectroscopy (FTIR). Methods: All 15 newly synthesized compounds (3a-3o) were subjected to in-vitro anti-microbial activity determination and compared with the known standard drug ciprofloxacin (1-2 μg/mL). Our in-silico analysis on the target protein, pdb id: 1d7u suggested that these analogues would be highly active against bacterial targets and thus, would act as good antimicrobial agents. Results: All 15 newly synthesized compounds (3a-3o) displayed potent activity on various experimental microbial strains (1.0-1.4 μg/mL). Compound, 3k was obtained as the best docked compound against common bacterial target enzyme, (pdb id:1d7u). The standard, Ciprofloxacin, retained the docking score of -111.3 Kcal/mol with similar binding amino acid residues (LYS272 (Pi-cation); ALA A:245 (Pisigma); TRP A:138 (Pi-Pi); ALA A:112; and MET A:141 (Pi-alkyl)) as of inbound. Conclusion : We believe that our current study would shed more light on the development of potent bis(indolyl)methanes as antimicrobial agents.