Most drug delivery vehicles lack thrust that propels them to disease sites for payload delivery. Herein, a microrod comprising a zinc (Zn) core and a positively-charged poly(3,4-ethylenedioxythiophene) (PEDOT+) shell incorporating an anionic model drug, which form a “galvanic cell” in an electrolyte solution, is proposed as a battery-driven drug delivery device. Upon immersion of the proposed Zn-based batteries in a physiological environment, two sets of redox reactions that compete with each other in a manner determined by the local pH occur spontaneously. At low pH, the reduction of H+ to H2 bubbles, which are essential to propel the Zn batteries as micromotors, prevails, while at higher pH, the reduction of PEDOT+ to actuate galvanically payload release dominates. Observations in mice suggest that the self-powered Zn batteries may rapidly react and move in the gastric fluid after oral administration, considerably improving their penetration and retention in the mucus layer for localized drug release, similar to those directly injected into the subcutaneous tissue. None of the investigated tissues exhibits any significant inflammation or cell apoptosis, revealing that the developed Zn-based batteries have potential to serve as safe drug delivery devices.