An electrochemical sensor is a classical sensing and detection method, which has the advantages of high sensitivity, low cost, and easy operation. With the progress of material technology, the selectivity, stability, biosafety, and other parameters of electrochemical sensors are also improved accordingly. Over the course of more than half a century, early thumb-size electrochemical sensors have been scaled down to the size of a needle tip, and their measuring instruments have also gone from giant workstations to tiny portable devices. Due to the numerous advantages and efforts of many researchers, it has become one of the most preferred methods for a large class of biomedical sensors. This chapter will briefly introduce the electrochemical principle and common electrochemical measurement methods and discuss the construction and application of portable electrochemical sensing systems.