Herein we report a series of novel 8-hydroxyquinoline-5-sufonamide derivatives, which were synthesized, characterized and tested as antimicrobial agents in vitro. The reaction of the key intermediate 8-hydroxy-7-iodoquinoline-5-sulfonyl chloride with different secondary amines, aromatic amines, glycine and hydrazine hydrate, followed by reaction of hydrazide derivative  with various ketonic and mono acid anhydride compounds yielded the desired sufonamide derivatives. All the new compounds were characterized by spectral and elemental analyses. Some of the newly synthesized final compounds were evaluated for their in vitro antibacterial and antifungal activities against pathogenic strains. The preliminary screening results indicated that most of the compounds demonstrated moderate to good antibacterial and antifungal activities, comparable to the standard drugs.