Colorectal cancer is the abnormal growth of cells in colon or rectum. Recent findings have acknowledged the role of bacterial infection and chronic inflammation in colorectal cancer initiation and progression. In order to detect and treat precancerous lesions, new tools are required, which may help to prevent or identify colorectal cancer at an early stage. To date, several different screening tests are available, including endoscopy, stool-based blood tests, and radiology-based tests. However, these analyses either lack sensitivity or are of an invasive nature. The use of fluorescently labeled probes can increase the detection sensitivity. However, autofluorescence, photobleaching, and photodamage are commonly encountered problems with fluorescence imaging. Upconverting nanoparticles (UCNPs) are recently developed lanthanide-doped nanocrystals that can be used as light-triggered luminescent probes and in drug delivery systems. In this review, we comprehensively summarize the recent developments and address future prospects of UCNP-based applications for diagnostics and therapeutic approaches associated with intestinal infection and colorectal cancer.