Nickel plating electrolytes prepared by using a simple salt solution can achieve nickel plating on laser-induced graphene (LIG) electrodes, which greatly enhances the electrical conductivity, electrochemical properties, wear resistance, and corrosion resistance of LIG. This makes the LIG–Ni electrodes well suited for electrophysiological, strain, and electrochemical sensing applications. The investigation of the mechanical properties of the LIG–Ni sensor and the monitoring of pulse, respiration, and swallowing confirmed that the sensor can sense insignificant deformations to relatively large conformal strains of skin. Modulation of the nickel-plating process of LIG–Ni, followed by chemical modification, may allow for the introduction of glucose redox catalyst Ni2Fe(CN)6with interestingly strong catalytic effects, which gives LIG–Ni impressive glucose-sensing properties. Additionally, the chemical modification of LIG–Ni for pH and Na+monitoring also confirmed its strong electrochemical monitoring potential, which demonstrates application prospects in the development of multiple electrochemical sensors for sweat parameters. A more uniform LIG–Ni multi-physiological sensor preparation process provides a prerequisite for the construction of an integrated multi-physiological sensor system. The sensor was validated to have continuous monitoring performance, and its preparation process is expected to form a system for non-invasive physiological parameter signal monitoring, thus contributing to motion monitoring, disease prevention, and disease diagnosis.