Interaction of metal nanoparticles and metal nanocomposites with blood proteins is important from the perspectives of cytotoxicity and production of novel drug delivery systems. In this study, Ag-MgO nanocomposites were bio-modified by different concentrations of Artemisia haussknechtii medicinal plant and Protoparmeliopsis muralis medicinal lichen extracts. Determination of physicochemical properties of NCs were carried out by UV-Visible spectroscopy, scanning electron microscope (SEM), X-ray powder diffraction (XRD), and Fourier transform infrared (FT-IR) analyses. Antibacterial effects of NCs against methicillin-resistant Staphylococcus aureus (MRSA), E. coli ATCC 25922, and P. aeruginosa ATCC 27853 bacteria were measured by disc diffusion and minimum inhibition/bactericidal concentrations (MIC and MBC). Also, in final section, interaction of bio-modified NCs (BNCs) with hemoglobin (Hb) protein was surveyed by SEM, atomic force microscope (AFM), and FT-IR techniques. BNCs by plant extract (10%w/v) showed highest antibacterial effects on E. coli ATCC 25922 as inhibition zone diameter of (IZD) value of 20 ± 0.89 mm. Aggregation of Hb around BNCs was approved by mentioned analyses. This investigation illustrated contribution of various functional groups including thiol and imidazole groups in self-assembly of Hb surrounding BNCs.