Abstract A novel series of 11 C‐3– and N‐1–substituted oxoacetamide indole derivatives were synthesized by reacting with various aromatic amines and alkyl halides. These compounds were characterized by using various spectral techniques, ie , 1 HNMR, 1 HNMR‐D 2 O, 13 CNMR, UV, elemental analysis, IR, and mass spectrometery. In vitro , antimicrobial studies of resultant compounds were carried out against two bacterial strains, Pseudomonas aeruginosa and Pseudomonas oryzihabitans using disc plate method. All the tested compounds showed vital efficiency as antimicrobial agents against both the bacterial strains. The results revealed that synthesized indole derivative 2‐(1‐(3‐bromopropyl)‐1 H ‐indol‐3‐yl)‐ N ‐(2‐nitrophenyl)‐2‐oxoacetamide displayed the best antimicrobial activity as compared with all other synthesized compounds.