Nanoscale systems are currently under investigation for multiple different diagnostic and therapeutic applications. These systems can be used to identify pathologically changed tissues or to selectively deliver drugs to these sites; both applications have an extremely high potential to ameliorate therapeutic outcomes for patients. Tissues as well as single cells can be targeted because of the small size of these systems, which enables enhanced diagnosis and increased specificity of therapy. Drug loads can be delivered directly to the site of action, which can result in a reduction in incidence and severity of adverse systemic effects. Several nano-based platform technologies are currently under investigation for use in therapeutic approaches, mainly for anti-inflammatory and anti-cancer therapies. Although many nanoscale systems show promising therapeutic outcomes in preclinical studies, only a limited number are ready for clinical use. This Review will discuss the diverse nanomaterials currently available and the first specific uses for select gastroenterological and hepatological pathologies. The discussion of diagnostic and therapeutic applications will consider realities of market introduction of these sometimes very complex systems in light of remaining regulatory challenges and hurdles for industrial production.