Samarium doped hydroxyapatite (Sm:HAp), Ca 10−í µí±¥ Sm í µí±¥ (PO 4) 6 (OH) 2 (HAp), bionanoparticles with different í µí±¥ Sm have been successfully synthesized by coprecipitation method. Detailed characterization of samarium doped hydroxyapatite nanoparticles (Sm:HAp-NPs) was carried out using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR). The biocompatibility of samarium doped hydroxyapatite was assessed by cell viability. The antibacterial activity of the Sm:HAp-NPs was tested against Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus). A linear increase of antimicrobial activity of P. aeruginosa has been observed when concentrations of Sm:HAp-NPs in the samples with í µí±¥ Sm = 0.02 were higher than 0.125 mg/mL. For Sm:HAp-NPs with í µí±¥ Sm = 0.05 a significant increase of antibacterial activity on E. coli was observed in the range 0.5–1 mg/mL. For low concentrations of Sm:HAp-NPs (í µí±¥ Sm = 0.05) from 0.031 to 0.125 mg/mL a high antibacterial activity on Enterococcus faecalis has been noticed. A growth of the inhibitory effect on S. aureus was observed for all concentrations of Sm:HAp-NPs with í µí±¥ Sm = 0.02.