Historically, clays have been widely used for the treatment of wounds and to stop hemorrhaging. The aim of this study was to combine four natural clay minerals (kaolinite, glauconite, montmorillonite, and bentonite) with magnetite (Fe3O4) nanoparticles to produce Fe3O4–clay complexes with enhanced antimicrobial properties and chemopreventive activity against melanoma. The magnetite–clay complexes were synthesized by the chemical co-precipitation method and characterized using XRD, TEM, STEM-EDS, SEM, and SQUID magnetometer. Antimicrobial properties were determined by evaluation of MIC values. The most promising materials were also subjected to direct contact antibacterial test according to the OECD standard for porous materials. Cytotoxicity of the complexes towards melanoma cells and normal human skin fibroblasts was assessed by MTT assay. We performed XRD, which confirmed the formation of Fe3O4–clay complex materials. It was also proven that complexes exhibited superparamagnetic properties. Microbiological experiments clearly revealed that modification of natural clays with magnetite significantly boosted their antimicrobial properties. Fe3O4–montmorillonite and Fe3O4–bentonite showed the strongest antimicrobial activity. Moreover, the mentioned complexes had the ability to reduce the viability of melanoma cells by 35–40%, while exhibiting no cytotoxicity against the normal human fibroblast (BJ) cell line, which is an extremely desirable feature. Thus, it may be concluded that Fe3O4–montmorillonite and Fe3O4–bentonite complexes hold promise for use in the management of infected wounds and wounds after melanoma excision. Keywords: nanostructured materials; kaolinite; glauconite; montmorillonite; bentonite; cytotoxicity; wound healing