2-Alkoxy-4-(aryl)-5H-indeno[ 1,2-b] pyridine-3-carbonitriles (3a-e and 4a-e) were synthesized via multicomponent reaction from 2-aryl-methylidineindan-1-ones (1a-e), malononitrile and K2CO3 in ethanol and/or methanol. The structures of obtained compounds (3a-e and 4a-e) were characterized using the spectroscopic methods (NMR, IR) and elemental analysis. Addition, the in vitro antimicrobial activities of compounds (3a-e) were tested against the five human pathogenic bacteria. Penicillin G and Ceftriaxone antibiotics were used as positive control. The results were given as MIC values (minimum inhibition concentration), and compounds 3b-d showed very high activity against Escherichia coli 111.