A series of 1,2,4-triazole derivatives (1–17) was synthesized and evaluated for its antimicrobial and anticancer potentials. Antimicrobial screening of the synthesized compounds indicated that they were most potent against Aspergillus niger and compound 14 was found to be the most active. Compound 7 showed appreciable anticancer activity against HCT 116, a colon cancer cell line. QSAR analysis indicated the importance of topological parameter, valence third order molecular connectivity index (3χv) and electronic parameter, dipole moment (μ) in describing the antimicrobial activity of the synthesized compounds.