In an effort to develop potent antimicrobial a series of mannich bases of 2,5-disubstututed indoles were prepared for investigating their antimicrobial activities. All compounds were found to be significantly active against gram positive bacteria: S. aureus, B. subtilus Gram negative bacteria: E.coli, P.aeruginosa and fungal strains: C. albicans, A. niger by tube dilution method. Compound N-((2-(4-bromophenyl)-5-nitro-1H-indol-3-yl)methyl)-Nphenyl benzenamine (MB10) and N-benzyl-N-((2-(4-bromophenyl)-5-nitro-1H-indol-3-yl) methyl) (phenyl) methanamine (MB11) emerged as the best antimicrobial agent in the present study. The structure of the synthesized compounds was confirmed by physico-chemical characteristics and spectroscopic investigations. Docking results of these two compounds with COX-2 (PDB ID: 4COX) also exhibited a strong binding profile.