Photodetection techniques in the non-fluorescent regime when combined with nanotechnology offer promising new angles in diagnosing diseased conditions over conventional fluorescence-based imaging. In this study, we developed two types of spherical gold nanostructures: gold nanoshells and gold nanoparticles and used them to enhance optical backscattering signal in confocal reflectance microscopy and OCT as well as Raman signal in Raman spectroscopy respectively. The gold nanoshells were conjugated to anti-EGFR for targeted molecular imaging and the gold nanoparticles were made to self-assembled using a novel drop-dry approach to form a SERS-active monolayer film. We have shown that the gold nanoshells can elicit an optical contrast based on molecular expression of EGFR to discriminate cancer from healthy cells under confocal reflectance microscopy as well as to improve the OCT signal over tissue phantoms that model intrinsic tissue scattering. The SERS-active gold nanoparticles film have also shown to enhance Raman signal in molecular analytes and enabled the SERS spectra of saliva from to be distinguishable from healthy individuals to a specificity of 70%. These results have demonstrated the additional diagnostic values provided by gold nanostructures in existing non-fluorescence based photodetection techniques.