The present communication deals with synthesis of a new series of spiro-2-[30 -(20 -phenyl)-3H-indolyl]-1-aryl-3-phenylaziridines. Infrared (IR), 1 H nuclear magnetic resonance (NMR), mass spectral, and elemental analysis data corroborated the structure of all synthesized compounds. Synthesized compounds were screened for antimicrobial activity against a representative panel of Grampositive and Gram-negative bacteria. All newly synthesized compounds showed remarkable antimicrobial behavior. Structure–activity relationship (SAR) investigations were applied to investigate the correlation between the molecular refractive index (MR) parameter of the compounds and their biological activity profile. All compounds were subjected to acute toxicity studies to determine 50% lethal dose (LD50) values.