INTRODUCTION: FeO nanoparticles (FeO NPs) with multiple functionalities are intriguing candidates for various biomedical applications. MATERIALS AND METHODS: This study introduced a simple and green synthesis of FeO NPs using a low-cost stabilizer of plant waste extract rich in polyphenols content with a well-known antioxidant property as well as anticancer ability to eliminate colon cancer cells. Herein, FeO NPs were fabricated via a facile co-precipitation method using the crude extract of fruit peel as a green stabilizer at different weight percentages (1, 2, 5, and 10 wt.%). The samples were analyzed for magnetic hyperthermia and then in vitro cytotoxicity assay was performed. RESULTS: The XRD planes of the samples were corresponding to the standard magnetite FeO with high crystallinity. From TEM analysis, the green synthesized NPs were spherical with an average size of 13.42±1.58 nm and displayed diffraction rings of the FeO phase, which was in good agreement with the obtained XRD results. FESEM images showed that the extract covered the surface of the FeO NPs well. The magnetization values for the magnetite samples were ranging from 49.80 emu/g to 69.42 emu/g. FTIR analysis verified the functional groups of the extract compounds and their interactions with the NPs. Based on DLS results, the hydrodynamic sizes of the FeO nanofluids were below 177 nm. Furthermore, the nanofluids indicated the zeta potential values up to -34.92±1.26 mV and remained stable during four weeks of storage, showing that the extract favorably improved the colloidal stability of the FeO NPs. In the hyperthermia experiment, the magnetic nanofluids showed the acceptable specific absorption rate (SAR) values and thermosensitive performances under exposure of various alternating magnetic fields. From results of in vitro cytotoxicity assay, the killing effects of the synthesized samples against HCT116 colon cancer cells were mostly higher compared to those against CCD112 colon normal cells. Remarkably, the FeO NPs containing 10 wt.% of the extract showed a lower IC value (99.80 µg/mL) in HCT116 colon cancer cell line than in CCD112 colon normal cell line (140.80 µg/mL). DISCUSSION: This research, therefore, introduced a new stabilizer of fruit peel extract for the biosynthesis of FeO NPs with desirable physiochemical properties for potential magnetic hyperthermia and colon cancer treatment.