The present study reports the synthesis of some novel heterocyclic derivatives by reacting cyanoacetohydrazide 1 in a basic medium with different electrophilic reagents. Initially, its reaction with H2O2 afforded 1,2,3-triazine-4,6(1H,5H)-dione 4, which upon addition to benzylidene malononitrile under Michael's condition yielded 7-amino-4-oxo-5-phenyl-1,5-dihydro-4H-pyrano[2,3-d][1,2,3]triazine-6-carbonitrile 6. Azidolysis of cyanoacetohydrazide resulted in the formation of 5,8-dihydrotetrazolo[1,5-c][1,2,3]triazin-7-ol 9. On the other hand, heterocyclization of cyanoacetohydrazide with ethyl cyanoacetate and/or chloroacetyl chloride produced 2,5-dioxo-2,4,5,6-tetrahydro-1H-pyrazolo[1,5-b]pyrazole-3-carbonitrile 13 and 3,5-dihydroxy-1,2-dihydropyridazine-4-carbonitrile16 , respectively. The later undergoes [2+3] intermolecular cycloaddition to the heteroallene system produced 4-(1,2,4-thiadiazol-3-yl)-1,2-dihydropyridazine-3,5-diol 17. Furthermore, Knoevenagel condensation and intramolecular heterocyclization of cyanoacetohydrazide with benzaldehyde and acetylacetone afforded 3-hydroxy-5-phenyl-4H-pyrazole-4-carbonitrile 21 and 5,6a-dimethyl-3-oxo-1,2,3,6a-tetrahydro-3aH-furo[3,2-c]pyrazole-3a-carbonitrile 25, respectively. Intermolecular heterocyclization of cyanoacetohydrazide with diethyl oxalate and carbon disulphide gave 5-Hydroxy-2,3a-dihydropyrrolo[2,3-c]pyrazole-3,4-dione 28 and 4-hydroxy-1,3a-dihydro-3H-pyrazolo[3,4-c]isothiazole-3-thione 33, respectively. All reactions proceeded in good to excellent yields and the synthesized compounds were identified by different spectroscopic techniques. All the obtained compounds are virtually screened by molecular docking on the target protein 1KZN by the MOE for potency as antibacterial agent. Also, pharmacophore and ADME studies were applied. Efficient binding to the target protein was found for some of the synthesized compounds.