Electrochemiluminescence (ECL) is a powerful technology that is the triple point of chemical, electronic, and optical technologies. The ECL-based sensors attract enormous attention due to the unifying of the advantages of electrochemical and optical sensors. The development of ultrasensitive, rapid, highly specific, and cost-effective ECL sensors for detecting substances with human health and life is critical. Metal-Organic Frameworks (MOFs) is a kind of molecular crystalline material regarded as a promising candidate for application in ECL sensors after its great improvement because of the improved MOFs with particular merits such as large surface area, tunable pore scale, structural diversity, superior conductivity, water stability, low toxicity, and good biocompatibility. In this review, we emphasize discussing the applications of MOFs for ECL sensing detection of varying targets that are related to human health and life, such as metal ions, small molecules, nucleic acids, proteins, bacteria, and viruses. Then, the relationship between ECL performance and MOFs characters is sprinkled in the discussion of the representative example. Finally, we provide the potential opportunities and challenges faced by MOFs in the realm of ECL sensors, as well as the future perspectives.