Computerized oral prescription administration (COPA) devices, systems, and methods are provided. In one embodiment, a method of managing substance administration is provided. The method comprises receiving, by a substance management system, a dosage instruction for administering a substance to an intended user through a mouthpiece including a recess sized and shaped to receive a unique dentition of the intended user; receiving, by the substance management system, activity information associated with administering the substance to the intended user; and generating, by the substance management system, a record based on the received activity information.