Nanomaterials have excellent properties and have been used widely in chemical engineering, electronics, mechanics, environment, energy, aerospace, and many other fields in recent years. Besides, nanomaterials have attracted increasing attention in the biomedical field. The interactions between nanomaterials and protein molecules are not only significant to the basic science of the biomedical field, but also crucial for the evaluation of biomedical applications and biosafety of nanomaterials. The interfacial interactions between proteins and nanomaterials could induce a series of changes to the structures and functions of proteins, such as the transformation of protein conformations, and the modulation of aggregation states, which would influence the functions of the protein molecules. Interfacial interactions can also influence the physicochemical features of nanomaterials, including morphology, size, hydrophilicity/hydrophobicity, and surface charge density. In this review we explained the molecular level mechanisms for the interactions between nanomaterials and proteins at the interface based on the detection technologies, and discussed the changes in physical and chemical features, structures, and functions. We envision this review could be helpful for the deeper understanding of the complicated interactions between nanomaterials and proteins, and could be beneficial for promoting the healthy, safe, and sustainable development and application of nanomaterials in the biological and medical fields.