Disclosed herein are methods, systems, and devices for oral drug delivery. The method generally involves orally administering a drug delivery device to the subject in need of treatment and triggering iontophoresis. The drug delivery device includes one or more active agents for delivery to the subject. The method can include the step of delivering the active agent to the intestinal mucosa after iontophoresis is triggered at the site, or simultaneously as iontophoresis is applied at the site. After the active agent(s) are delivered, the drug delivery device can be released from the intestinal mucosa. The iontophoresis can be performed for a period of time and at an electrical current that is effective to improve permeability of the one or more active agents across the intestine compared to orally administering the same drug delivery device in the absence of iontophoresis.
