Novel 2-[(benzalamino-4-hydroxybenzyl) [1,3,4]-oxadiazino[6,5-b]]indole derivatives (V1-21) were synthesized via a simple condensation reaction between 2-Amino-4-([1,3,4]-oxadiazino-[6,5-b]indole-3-yl)-phenol (IV) and challenging aromatic aldehydes. The compound IV was synthesized by an acid catalyzed cyclization of 3-amino-4-hydroxy-benzoic acid (2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazide (III). Thus produced final compounds (V1-21) were purified using column chromatography and then characterized by various spectroscopic techniques. Finally, the title compounds were screened for antimicrobial activity and shown promising results when compared with standard compounds. Key words: [1,3,4]Oxadiazine-[5,6-b]indole, aromatic aldehydes, antimicrobial activity.