A series of novel substituted 6′-(4-chlorophenyl)-3,4′-bipyridine-3′-carbonitriles with incorporated pyrazole and/or triazole moieties have been synthesized using 2-(6′-(4-chlorophenyl)-3′-cyano-3,4′-bipyridin-2′-yloxy)acetohydrazide (3) as starting material. Also, the key intermediate 3 reacted with aromatic aldehydes and tosyl chloride to give the corresponding Schiff bases and tosyl hydrazide derivatives, respectively. The antimicrobial of these newly synthesized compounds was evaluated against Bacillus subtilis as Gram-positive bacteria and Trichoderma viride as a fungus; some of these compounds such as 5, 6, 7, 8, 10, 12, and 14 showed excellent activities as antimicrobial agents. Moreover, the cytotoxic activity of the most active compounds was assessed in vitro against human tumor liver cancer cell line (HEPG2); compounds 8, 10, 13a, and 14 showed potent activities relative to Doxorubicin which was used as a reference standard drug in this study.