Optical coherence tomography (OCT) is a widely used structural imaging method. However, it has limited use in molecular imaging due to the lack of an effective contrast mechanism. Gold nanoparticles have been widely used as molecular probes for optical microcopy based on Surface Plasmon Resonance (SPR). Unfortunately, the SPR enhanced backscattering from nanoparticles is still relatively weak compared with the background signal from microscopic structures in biological tissues when imaged with OCT. Consequently, it is extremely challenging to perform OCT imaging of conventional nanoparticles in thick tissues with sensitivity comparable to that of fluorescence imaging. We have discovered and demonstrated a novel approach towards remarkable contrast enhancement, which is achieved by the use of a circular-polarization optical coherence microscopy system and 3-dimensional chiral nanostructures as contrast agents. By detecting the circular intensity differential depolarization (CIDD), we successfully acquired high quality images of single chiral nanoparticles underneath a 1-mm-thick tissue -mimicking phantom.