The present study focuses on the effects of the physicochemical properties of superparamagnetic PEG-modified, positively charged and negatively charged iron oxide nanoparticles (SPIONs) on their reactivity with hydrogen peroxide. Our hypothesis was that the reactivity of SPIONs in this reaction would depend on their surface properties. The comparative study of the nanoparticles with DLS and TEM revealed the average sizes of PEG-modified, positively charged and negatively charged SPIONs. We observed that the reactivity of negatively charged SPIONs with hydrogen peroxide was less than that of positively charged SPIONs and that of these second nanoparticles was less than that of PEG-modified SPIONs. This difference in the reactivity of these SPIONs with hydrogen peroxide was attributed to the presence of carboxyl or amine groups on their surface. However, the values of the rate constants of the reactions of PEG-SPIONs, positively charged SPIONs and negatively charged SPIONS with hydrogen peroxide showed that the reaction of negatively charged SPIONs with hydrogen peroxide was more rapid than that of PEG-SPIONs and the reaction of this second SPIONs with hydrogen peroxide was more rapid than that of positively charged SPIONs. The surface study of the SPIONs using XPS showed that the high resolution spectra of these nanoparticles changed after reaction with hydrogen peroxide, which indicates their surface modifications. These investigations can help develop more appropriate nanoparticles with controlled physicochemical properties.