© 2019, The Author(s). We present a comparative study of the toxicity of polyethylene glycol (PEG)–coated cobalt ferrite nanoparticles and nanospheres. Nanoparticles were prepared by hydrothermal method while nanospheres were prepared by solvothermal technique. The surface of nanomaterials was successfully modified with polyethylene glycol. To investigate the morphology of the prepared samples, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, thermogravimetric analysis (TGA), and electron microscopy techniques were employed. Structural analyses confirmed the formation of polycrystalline cobalt ferrite nanoparticles with diameters in the range 20–25 nm and nanospheres in the range 80–100 nm, respectively. Kunming SPF mice (female, 6–8 weeks old) were used to investigate the toxicity induced by cobalt ferrite nanoparticles and nanospheres in different organs of the mice. Biodistribution studies, biochemical indices, histopathological assessments, inflammatory factors, oxidation and antioxidant levels, and cytotoxicity tests were performed to assess the toxicity induced by cobalt ferrite nanoparticles and nanospheres in mice. Cobalt ferrite nanospheres were found to be more toxic than the nanoparticles and curcumin was proved to be a good healing agent for the toxicity induced by PEG-coated cobalt ferrite nanomaterials in mice.