Non-invasive high-resolution biophotonics imaging technologies, such as optical coherence tomography (OCT), two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging, have emerged as a new imaging modality with a great translational potential for clinical applications, including detection of diseases at early stages, guidance of surgical interventions and monitoring of therapeutic effects. These technologies are capable of revealing structural, functional, and potentially molecular or biochemical information about biological tissues in real time with a resolution approaching conventional histology but without the need for tissue removal. Clinical translation of these high-resolution imaging technologies faces two critical challenges: (1) the need for enabling endomicroscopes/fiber-optic sensors that permit assessment of internal organs, and (2) the need for methods to enhance the limited intrinsic molecular contrast between normal and disease tissue. In this seminar, we will report on our recent research on developing ultrathin fiber-optic endomicroscopy technology, which is instrumental for translating OCT, TPF and SHG imaging into the clinic. We will also discuss our initial attempt to improve molecular sensitivity and specificity by development of innovative structured metallic and micellar nanoparticles which are potentially clinically translatable. In addition, we will present some exemplary applications of these biophotonic imaging technologies, including (1) assessment of normal and stimulated tissue regeneration processes, and (2) detection of abnormalities in the gastrointestinal tract (such as Barrett's, subsquamous Barrett's epithelium and cancer).