Sm3+-doped magnetic nanoparticles (NPs) were prepared via microwave-assisted polyol synthesis in ethylene glycol, poly(ethylene glycol) and mixed ethylene glycol—poly(ethylene glycol) solutions. In present work, the effects of organic solvent composition on particle size, particle size distribution, extent of agglomeration, and samarium content in prepared NPs were studied. The synthesized NPs were characterized by several techniques as follows: X-ray diffraction (XRD), transmission electron microscopy (TEM), thermogravimetry (TGA) and X-Ray fluorescence (XRF) analysis. XRD and TEM results showed formation of ~6.0–17.9 nm NPs having different microstructure characteristics (average particle size, particle size distribution, and agglomeration). The TGA analysis indicated the presence of organic components on the surface of NPs. Cytotoxic activity of the prepared magnetic NPs towards HeLa cells was evaluated by using standard live/dead assay in comparison to a control solution. It was shown that prepared magnetic NPs are characterized by low toxicity that makes possible their use for biomedical applications. © 2016, Springer Science+Business Media New York.