A new series of azo-azomethine compounds derived from sulfadiazine were prepared. The compounds were prepared, starting from the coupling of the sulfadiazine diazonium salt with 2- hydroxy -3- methoxy benzaldehyde, followed by condensation with 4-bromoaniline, 2- chloroaniline, 2- methyl-3-chloroaniline, sulfadiazine, 2,4-dimethylaniline, and 2- hydroxyaniline, respectively. All compounds were characterized by CHN analyses, FT-IR, and NMR spectroscopic data. The antimicrobial activity of all synthesized compounds was studied against gram-positive and gram-negative bacteria and fungi. They were screened for their antibacterial activities towards the gram-positive Staphylococcus aureus and the gram-negative Escherichia coli, as well as their antifungal activities against Aspergillus niger, candidaalbicane, and Candida glabrata, to evaluate their antimicrobial potential. Furthermore, their antioxidant activities were investigated by using the β – Carotene bleaching method. QSAR Properties and Molecular properties of all compounds were obtained by using Hyperchem software.