There is a continuous need for discovering new nanomaterials with antibacterial activity against various pathogens, like Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This study was performed to assess the antimicrobial activity of two novel nanostructured forsterites, both in the absence and the presence of silver nanoparticles (AgNPs). The two nano forsterites (FS) were prepared by advanced sol-gel (FSsg) and precipitation (FSpp) methods. Preparation of colloidal AgNPs systems was realized by using the precursor, AgNO3, and the trisodium citrate and tanic acid assuring the formation and stabilization of AgNPs. The characterization of nano forsterite powders was carried out using complementary physical methods: XRD, SEM, and AFM. The AgNPs were characterized by UV-Vis spectra, STEM and AFM imaging. The antimicrobial activity was studied by the agar well diffusion method both in the FS native state, as FSsg and FSpp, and in their mixture with silver nanoparticles (AgNPs). The inhibitory effect of synthesized forsterites, FSsg and FSpp, particularly variants with AgNPs was found only on the S. aureus strain, the zones of inhibition being between 8 and 10 mm, and more intensely expressed in the FSpp-AgNPs dispersions. These findings open new orthopedic applications of these systems, particularly for antimicrobial coated metallic implants.