Oral iron supplements such as ferrous iron salts are major treatment agents for iron deficiency anemia ( IDA) due to the convenience of large dose administration and good patient compliance. However, the gastrointestinal adverse impact caused by Fe2+ stimulus and low bioavailability severely impedes its therapeutic effects. In recent years, it has been found that nano iron-based nanoparticles with high surface-to-volume ratio and low iron ion leakage can alleviate the toxic effect and improve the gastrointestinal absorbance. For further clinical development, nano materials need to meet the pharmaceutical quality demand. Carboxymethyl cellulose ( CMC ) is a significant pharmaceutical ingredient applied in approved drug formulations, and polyglucosorbitol carboxymethylether ( PSC) has been utilized in iron-based nanomedicine ferumoxytol synthesis, both of which can be firmly anchored on iron oxide by carboxyl chelation. In this work, iron oxide nanoparticles ( NPs) modified with CMC were designed and synthesized, and the structure composition and physicochemical properties were distinctly characterized. Oral supplement effects on rat IDA were investigated and compared with other recently reported iron supplements including NPs modified with PSC. Results show that the oral nano iron supplement achieved the recovery of hemoglobin and serum iron level in only two weeks with high safety. The nano iron oxide modified with pharmaceutical excipients provides new potential approach for oral iron supplement available in clinics.