Nanozymes, which can be defined as nanomaterials with excellent catalytic function, are well known to the scientific community due to their distinct merits, such as low cost and high stability, which render them preferable to natural enzymes. As porous organic-inorganic coordination materials, metal-organic frameworks (MOFs) possess a large number of active sites and thus can effectively mimic the properties of natural enzymes. Recently, MOF-based nanozymes have also exhibited good application potential for the analysis of heavy metal ions. In comparison to the traditional detection methods for heavy metal ions, nanozyme-based colorimetric sensing permits intuitive visual analysis by using relatively simple instruments, facilitating rapid and simple on-site screening. In this minireview, the preparation of MOF-based nanozymes and the different nanozyme activity types are briefly described, such as peroxidase-like and oxidase-like, and the relevant catalytic mechanisms are elaborated. Based on this, different response mechanisms of MOF-based colorimetric methods to heavy metal ions, such as turn-off, turn-on, and turn-off-on, are discussed. In addition, the colorimetric sensing applications of MOF-based nanozymes for the detection of heavy metal ions are summarized. Finally, the current research status of MOF-based nanozymes and the future development direction are discussed.