A series of twenty-eight Phthalimide/Naphthalimide containing 1,2,3-triazole hybrids (6a-6z2) have been synthesized based on hybrid pharmacophore concept through Click reaction of terminal alkynes (3a-3d) with aromatic azides (5a-5 g). All the synthesized Phthalimide/Naphthalimide containing 1,2,3-triazole hybrids were characterized utilizing various spectral techniques like 1D, 2D NMR, FTIR and HRMS. Further, the structure of synthesized compound 6b (CCDC 2,192,005) was also confirmed by Single Crystal X-ray Crystallography. Additionally, In vitro antimicrobial activity of the synthesized hybrids were performed against two Gram positive bacterial strains and two Gram negative bacterial strains as well as two parasitic strains by serial dilution technique. The compound 6e (MIC 0.0179 μmol/mL) demonstrated excellent antimicrobial potency due to presence of nitro group on phenyl ring against all tested strains. The binding conformation of the most potent Phthalimide/Naphthalimide containing 1,2,3-triazole hybrid 6e with E. coli topoisomerase II DNA gyrase B was ascertained by molecular docking studies.