Phototherapy is widely applied to various human diseases. Nanomedicine-based phototherapy can be classified into photodynamic therapy (PDT) and photothermal therapy (PTT). Activated photosensitizer kills the target cells by generating radicals or reactive oxygen species in PDT while generating heat in PTT. Both PDT and PTT have been employed for treating various diseases, from preclinical to randomized controlled clinical trials. However, there are still hurdles to overcome before entering clinical practice. This review provides an overview of nanomedicine-based phototherapy, especially in non-oncologic diseases. Multiple clinical trials were undertaken to prove the therapeutic efficacy of PDT in dermatologic, ophthalmologic, cardiovascular, and dental diseases. Preclinical studies showed the feasibility of PDT in neurologic, gastrointestinal, respiratory, and musculoskeletal diseases. A few clinical studies of PTT were tried in atherosclerosis and dry eye syndrome. Although most studies have shown promising results, there have been limitations in specificity, targeting efficiency, and tissue penetration using phototherapy. Recently, nanomaterials have shown promising results to overcome these limitations. With advanced technology, nanomedicine-based phototherapy holds great potential for broader clinical practice.