Abstract Electromyography (EMG) is a widely used diagnostic technique for evaluating the electrical activity of muscles and their controlling nerves. However, conventional surface electrodes with planar structures often suffer from low spatial resolution and suboptimal signal quality. Here, 3D‐shaped, substrate‐free, soft, and biocompatible liquid metal electrodes (LMe) are presented as a wearable interface for neuromuscular signal recording. These electrodes enable the acquisition of high‐quality EMG signals while their intrinsic mechanical softness supports long‐term use in clinical settings. In a human pilot study, continuous, high‐spatial‐resolution EMG monitoring of musculoskeletal activity over 25 days is achieved. Furthermore, in vivo EMG monitoring in mouse models of ischemia and volumetric muscle loss demonstrated the therapeutic effects of extracellular muscle‐rehabilitative drugs. This work highlights the potential of LMe for advanced drug screening and long‐term clinical diagnostics.