Novel Schiff bases of N-substituted isatin, 1–13, were synthesized starting from isatin and N-(4-amino-2 methylphenyl)-4-chlorophthalimide and their structures were confirmed by spectral and elemental analyses. All new compounds were tested for their in vitro antibacterial activity against a range of Gram ?ve bacterial strains, like Bacillus subtilis (NCIM-2156), Staphylococcus aureus (NCIM-2079) and Staphylococcus epidermis (NCIM-2493) and Gram -ve bacterial strains, like Pseudomonas aeruginosa (NCIM-2036), Escherichia coli (NCIM-2065) and Proteus vulgaris (NCIM-2027) following broth dilution method as recommended by the National Committee for clinical laboratory standards using ciprofloxacin as reference. Determination of minimum inhibitory concentration (MIC) and zone of inhibition showed that the molecules were more active against Gram -ve bacteria than Gram ?ve bacteria. The compounds showed promising antibacterial properties with MIC ranging between 10 and 30 lg/mL.