<p>Cellular forces critically regulate physiology and pathology—including cell shape, proliferation, migration, and immune responses. However, conventional mechanosensing techniques lack the spatial resolution and non-invasiveness needed to monitor these forces in living cells in real time. DNA nanotechnology overcomes these limitations through programmable design, piconewton force sensitivity, and inherent biocompatibility, enabling transformative platforms for next-generation mechanical sensors. This review synthesizes a decade of progress in DNA-based molecular force sensors, examining their structural designs, mechanotransduction mechanisms, and applications in force mapping, super-resolution imaging, and dynamic tracking at membrane receptors, extracellular microenvironments, and intercellular junctions. We further highlight how these advances will catalyze mechanopharmacology and clinical diagnostics via high-throughput mechanoreceptor screening and mechanoresponsive drug delivery systems.</p>