Nanotechnology investigation is generating extraordinary improvements for identifying, treating, and avoiding health problems. However, while nanoparticles can mainly to breakthrough applications, they may also root for dangerous side effects. It has been revealed that nanomaterials can enter the human body through a number of ports. Nanoparticle can modify the physiochemical properties of material as well as create the opportunity for increased the uptake and interaction with biological tissue through inhalation ingestion and injection. This combination effects generate adverse biological effects in living cell. Health effects of nanoparticles are attracting extensive and increasing concern of the public and government worldwide. So far, most of the nanotoxicity investigation concentrated on respiratory tract contacts for considering the health effects of nanoparticles. Other exposure routes, e.g., gastrointestinal tract also need to be considered as potential portals of entry. We review the recent accepting threat of NPs resulting from the novel science of nanotoxicology and the restricted exploration to date into human contact to these particles.