The structures of Schiff-base compounds (A and B) derived from the ceftriaxone drug were determined using spectroscopic techniques. The synthesis started by starting a chemical reaction between ceftriaxone and the suitable substituted benzaldehydes such as 4-dimethylaminobenzaldehyde and 4-chlorobenzaldehyde. The antimicrobial activities of Schiff base compounds containing the ceftriaxone moiety were assessed in vitro against two types of bacteria: gram-positive microorganisms (Bacillus subtilis and Enterococcus faecalis) and Candida and Asperigillus nigaer at varying concentrations (50 and 100 M). The findings indicated that some derivatives had favorable antibacterial efficacy in comparison to the parent drug (ceftriaxone), whereas amoxicillin drug showed significant biological potency.