Magnetic Fe3O4 nanoparticles (MNPs) are becoming more important every day in drug targeting. We prepared here MNPs in a simple one-step reaction by following the solvothermal method assisted by azide and alkyne functionalized polyethylene glycol (PEG400) polymers, as well as by PEG6000 and the polyol -cyclodextrin (CD). The composition, morphology, and structure of the nanospheres were characterized using Transmission Electron Microscopy (TEM), Nuclear Magnetic Resonance (NMR), X-Ray Diffraction Diffractometry (XRD), Atomic Force Microscopy (AFM), Fourier-Transform Infrared Spectroscopy (FT-IR), Matrix-Assisted Laser Desorption/Ionization (MALDI) and Vibrating Sample Magnetometry (VSM). The obtained nanoparticles (@Fe3O4-PEGs and @Fe3O4-CD) showed diameters between 90-250 nm, depending on the polymer used and the Fe3O4·6H2O precursor concentration, typically, 0.13 M, 200 °C, and 24 h of reaction. MNPs exhibited superparamagnetic properties with high saturation of magnetization at room temperature, reaching values of 59.9 emu/g (@Fe3O4-PEG6000), and no ferromagnetism. Likewise, they showed temperature elevation after applying an alternating magnetic field (AMF) in all cases, obtaining Specific Absorption Rate (SAR) values of up to 51.87 ± 2.23 W/g in the case of @Fe3O4-PEG6000. Both PEGs and the βCD played a crucial role as electrostatic stabilizers in the formation of Fe3O4 nanospheres, providing a polymeric/polyol coating around the magnetic cores. Additionally, the formed systems are susceptible for click chemistry, as was demonstrated in the case of the cannabidiol-propargyl derivative (CBD-Pro), which was synthesized and covalently attached to the azide functionalized surface of the system @Fe3O4-PEG400-N3. Prepared MNPs are highly dispersible in water, remaining in suspension for over 3 days, and non-toxic in the T84 human colon cancer cell line, indicating that they are ideal candidates for biomedical applications.