Peripheral neuromodulation has been widely used throughout clinical practices and basic neuroscience research. However, the mechanical and geometrical mismatches at current electrode-nerve interfaces and complicated surgical implantation often induce irreversible neural damage, such as axonal degradation. Here, compatible with traditional 2D planar processing, we propose a 3D twining electrode by integrating stretchable mesh serpentine wires onto a flexible shape memory substrate, which has permanent shape reconfigurability (from 2D to 3D), distinct elastic modulus controllability (from ~100 MPa to ~300 kPa), and shape memory recoverability at body temperature. Similar to the climbing process of twining plants, the temporarily flattened 2D stiff twining electrode can naturally self-climb onto nerves driven by 37°C normal saline and form 3D flexible neural interfaces with minimal constraint on the deforming nerves. In vivo animal experiments, including right vagus nerve stimulation for reducing the heart rate and action potential recording of the sciatic nerve, demonstrate the potential clinical utility.