The detection of active substances in the body is very important for good human health as it gives important insights into the smooth functioning of the body. Most of the conventional materials that can be used as suitable probes require complicated fabrication methodologies, have poor stability and are susceptible to environmental effects. In contrast, metal-organic frameworks (MOFs) offer unique advantages as probes for testing analytes due to their tunable porosity, good specific surface area and ease of modification. Unlike previously reported perspectives/reviews, this perspective focuses on the latest applications of MOFs as detection materials for hydrogen peroxide, various metal ions, hydrogen sulfide, organic small molecules, glutathione, and organic macromolecules such as nucleic acids, and focuses on providing a more detailed mechanism of action. Also, the basic principles of action utilized by this class of materials are discussed.