An electrowetting-based pH-responsive valve that uses a nonstandard electrochemical three-electrode system is proposed. The system comprises a gold valve electrode and an iridium electrode that act as the working and auxiliary electrodes, depending on the purpose, while an iridium oxide pH-sensitive electrode acts as the reference electrode. To make the valve open at pH higher than a threshold, the gold valve electrode is used as the working electrode and a voltage is applied to it with respect to the pH-sensitive reference electrode. To make the valve open at pH lower than the threshold, the gold valve electrode is used as the auxiliary electrode, while the iridium electrode is used as the working electrode. The wettability of the valve electrode is altered when a voltage is applied to it. When the pH of a solution crosses the threshold, the potential of the gold valve electrode exceeds a threshold potential because of the change in the potential of the pH-sensitive reference electrode. Consequently, the gold valve electrode becomes more hydrophilic, thereby allowing the solution to pass through the valve. Furthermore, by combining two valve electrodes, we realized a pH filter that allows solutions with pH within a limited range to pass through it. Urea- and glucose-responsive valves that opened at concentrations higher than the threshold could also be formed by immobilizing an enzyme on the pH-sensitive reference electrode.