Microwave-assisted organic synthesis, a green chemistry approach, is nowadays widely used in the drug synthesis. Microwave-assisted synthesis improves both throughput and turnaround time for medicinal chemists by offering the benefits of drastically reduced reaction times, increased yields, and pure products. Schiff bases are the important class of organic compounds due to their flexibility, and structural diversities due to the presence of azomethine group which is helpful for elucidating the mechanism of transformation and rasemination reaction in biological system. This novel compound could also act as valuable ligands for the development of new chemical entities. In the present work, some Schiff bases of Isatin derivatives was synthesized using microwave heating method. Schiff base of Isatin were synthesized by condensation of the keto group of Isatin with different aromatic primary amines. They were characterized by means of spectral data and subsequently subjected to the in vitro antibacterial activities against gram positive and gram negative strains of microbes. It was observed that the compound with electron withdrawing substituents exhibited good antibacterial activities against almost all the micro organisms.