This study presents the preparation of hybrid iron oxide nanocomposites through a two-step process combining microfluidic-assisted synthesis and post-synthetic surface modification. FeO nanoparticles were synthesized and simultaneously functionalized with salicylic acid using a three-dimensional vortex-type microfluidic chip, enabling rapid and uniform particle formation. The resulting FeO/SA nanostructures were further modified with either silver or copper oxide to form iron oxide nanocomposites with enhanced antimicrobial functionality. These nanocomposites were subsequently integrated into silica aerogel matrices using a dip-coating approach to improve surface dispersion, structural stability, and biocompatibility. The structural and morphological properties of the samples were investigated using XRD, FT-IR, TEM with SAED analysis, and Raman microscopy. In vitro cytotoxicity and antimicrobial assays demonstrated that FeO/SA-Ag and FeO/SA-CuO exhibit potent antibacterial activity and cell type-dependent biocompatibility. In vivo biodistribution studies showed no accumulation in major organs and selective clearance via the spleen, validating the systemic safety of the platform. These findings highlight the potential of the synthesized nanocomposites as biocompatible, antimicrobial coatings for advanced biomedical surfaces.