The present study synthesized a series of 1,3,4-oxadiazinoindole moiety-containing compounds by combining MAOI’s hydrazide moiety and tricyclic moiety having antidepressant activity. The formation of amino acid chloride from amino acids started the synthesis. Further, they were converted into amino acid hydrazide, and then amino acid hydrazones were prepared by reaction of amino acid hydrazide with isatin. Finally, cyclization was acted on hydrazone-containing compounds in the presence of cold H2SO4. Synthesized compounds are characterized and confirmed via mass spectroscopy, 1H-nuclear magnetic resonance strategies, fourier transform infrared spectroscopy, thin layer chromatography, and melting point. The compounds were evaluated for antidepressant activity.