A new series of novel triazolothiadiazepinylindole analogues were synthesized with an aim to examine possible antioxidant and antimicrobial activities. The titled compounds (3a-z) were obtained in good yield by reacting 5-(5-substituted-3-phenyl-1H-indol-2-yl)-4-amino-4H-1,2,4-triazole-3-thiols 1a-c with 3-(2,5-disubstituted-1H-indol-3-yl)-1(4-substituted phenyl)prop-2-en-1-ones 2a-i. All the newly synthesized compounds were characterized by IR, (1)H NMR, mass spectroscopic and analytical data. The synthesized analogues were tested for antioxidant and antimicrobial potency. Among the tested compounds 3a-c and 3j-l have shown very promising free radical scavenging activity and total antioxidant capacity. Compounds 3d-f, 3m-o, and 3s-z have shown excellent ferric reducing antioxidant activity. An outstanding antimicrobial activity is observed with compounds 3a-c and 3j-l.