Using a series of chemical reactions, several quinoxalinone derivatives bearing chemically different moieties such as substituted acetanilido, arylideno, phthalimido, thiadiazolo and pyrazolo were prepared to study their antimicrobial activity. The structures of the new compounds were established using elemental and spectral analyses. The antimicrobial susceptibility testing of some hovel compounds were carried out whereas some of them showed activity against Gram-positive rods only.