This chapter discusses the design and construction of surface-enhanced Raman scattering (SERS) active nanostructures with tunable size-/shape- dependent physical and chemical properties, and provides examples of exploit their wide applications in many scientific and technological fields. Coupled with biomolecules, different hybrid devices were developed, which offered a powerful platform to study the conformation change, dynamic behavior and biocatalysis of the target redox proteins like cytochrome c (Cyt-c, usually as a model protein). It would be benefit to deeply understand the relationship of the structure and function in biological system. Moreover, these hybrid devices could serve as an optical handle to investigate the properties of the structures themselves, such as how to control their optic-/electric- response for spectroelectrochemistry, which are widely used in (bio)analytical chemistry and interfacial science. In this field, the (electro)depositon of novel SRES-active (bio)structures directly on electrodes become a highlight and exciting goal, which produces inexpensive, controllable, reproducible, reusable biointerfaces by tailoring the morphology of the deposits, biomolecules, or combined both together. This chapter reviewed recent advances in the construction and applications of the biomaterials, mainly contributed by our laboratory in the latest five years. We roughly describe several typical optobioelectronic devices, which combine biotechnology with optical (eg. surface enhanced resonance Raman scattering, SERRS) and electrochemical techniques, while the rapid progress of the nanotechnology provides extra opportunities for investigations in this field. Firstly, we discussed the recent development of the SERSactive nanostructures. These nanostructures are functionalized with biocompatible coatings focused on different mecaptoalkanes for efficient immobilization of the target protein. Then, these biosensing devices were applied to study the conformation change, redox behavior and biocatalysis of the immobilized proteins. Besides, the electron transfer mechanism of the protein with the conventional electrode was also discussed, according to the experiments and interfacial bioelectrochemistry theory. Furthermore, the comparable results, obtained from spectro-electrochemistry experiments, are explored and discussed in some detail. Finally, some significant advances combined electrochemistry with surface-sensitive SERS for the nanostructured biointerfaces are also outlined.