Abstract <p>Schiff base ligands and their coordination complexes with transition metals have garnered significant interest in medicinal chemistry due to their diverse biological activities, particularly antimicrobial properties. Among them, Fe(II) and Fe(III) complexes have shown remarkable potential as antimicrobial agents against a broad spectrum of pathogens. This review highlights recent advances (2020 to 2025) in the antimicrobial evaluation of Fe(II) and Fe(III) Schiff base complexes. Key studies reporting improved efficacy against bacterial and fungal strains are examined, with a focus on structural variations of ligands, coordination geometries, and the influence of metal oxidation states on bioactivity. A central theme of this review is the role of complexation in enhancing antimicrobial activity. The process of forming metal–ligand complexes has been shown to improve membrane permeability, increase reactive oxygen species (ROS) generation, and inhibit essential microbial enzymes. Additionally, the electronic and steric properties of the Schiff base framework significantly affect metal chelation and, in turn, biological performance. By correlating molecular design with antimicrobial outcomes, this review offers valuable insights into structure–activity relationships and highlights future directions for developing iron-based metallopharmaceuticals with enhanced therapeutic potential.</p>