<b><i>Background:</i></b> Gastrointestinal malignancies have the greatest incidence and cancer-associated death rates worldwide. Routine therapeutic modalities include surgery, chemotherapy and radiation but they often fail to reach the goal of cancer-free survival. <b><i>Summary:</i></b> In the light of this urgent medical need for the treatment of GI tumors, nanotech­nology-based approaches, i.e. nanomedicine, promise new therapeutic options. Using nanoparticles instead of classically designed drugs, targeting anticancer agents directly to the tumor site may revolutionize both diagnostic and therapeutic tools thereby facilitating the identification and elimination of malignant cells. Importantly, diagnostic insight and therapeutic effects can be achieved simultaneously through the same nanoparticle. Additionally, a nanoparticle may be loaded with more than one agent, thereby further increasing the value and power of the nanotechnology approach in oncologic therapeutic concepts. Although most insight into mechanisms of nanomedicine has been gained from in vitro and preclinical in vivo models, few clinical trials have been conducted, and nanomedicine-based concepts are already part of standard treatment algorithms. However, despite substantial progress it remains a challenge to design nanoparticles that feature all desirable characteristics at the same time. <b><i>Key Messages:</i></b> This review seeks to provide substantial insight into the current status of nanomedicine-based approaches employed for diagnostic and/or therapeutic purposes in the field of gastrointestinal cancers by highlighting achievements and pointing out unresolved issues that need to be further addressed by future research attempts.