Here an attempt has been made to synthesize fourteen 5-methylpyrazine-2-carbohydrazide derivatives. The synthesized derivatives were assessed for their in-vitro anti-bacterial activity and minimum inhibitory concentration (MIC) against Gram-positive strains (Staphylococcus aureus and Bacillus subtilis) and Gram-negative strains (Salmonella typhi and Escherichia coli). During the present work, 5-methylpyrazinoic acid was esterified with ethanol to get ethylpyrazinoate and it refluxed with hydrazine hydrate to yield the 5-methylpyrazinoic acid hydrazide. The obtained acid hydrazide was then condensed with various substituted aromatic aldehydes to yield various 5-methylpyrazine-2- carbohydrazide derivatives. The structures of newly synthesized compounds so obtained were confirmed by using IR, 1HNMR, MS spectral data. All compounds gave satisfactory elemental analyses. The compounds PM 8-10, (i.e. 2,3 and 4- nitro benzaldehyde derivatives respectively) showed promising activity amongst the compounds tested against both the Gram-positive and Gram-negative strains tested. .