Metal ions play crucial roles in biological processes, and their dysregulation can lead to various diseases. Understanding the distribution of these metal ions provides deeper insight into their roles in both health and disease. DNAzymes offer a general approach for detecting nearly any metal ion within cells and with high sensitivity and selectivity, including different oxidation states of the same metal ion. This Review summarizes recent developments in signal transduction strategies for DNAzyme-based sensing and imaging of metal ions in living cells and . We examine various signal transduction strategies to convert metal ion binding by DNAzymes into measurable signals. These strategies include fluorescence imaging using small molecules, nanostructures and nanoparticles, motors and machines, and other fluorescent materials as well as bioluminescence imaging. We then provide recent examples of applying these DNAzyme-based fluorescence or bioluminescence imaging methods to understand metal ion dynamics and their roles in diseases in living cells and . Finally, we discuss future directions for advancing intracellular and metal ion imaging using DNAzymes.