Infectious diseases caused by protozoa, viruses, bacteria and other agents may be transmitted to people world-wide which relates over 17 million death annually. The treatment of the diseases is hampered mainly by blood brain barrier, multi-drug resistance, drug- toxicity, insolubility and poor bioavailability. To overcome these barriers, currently iron oxide nanoparticles (IONPs) have gained attraction owing to their unique characteristics such as nanosized high surface to volume ratio, low cost easy synthesis methodology, microbicidal and anti-carcinogenic activities, surface modification capability, components-vectoring ability, photothermal and superparamagnetism features for generating reactive oxygen species, non-oxidative induction and metal ion release to disrupt cells. This review demonstrates the current advances regarding their synthesis, functionalization, mechanism of action, biodistribution and elimination for the application in targeted delivery and therapy against various diseases.