Computerized oral prescription administration with refillable medication dispensing devices and associated systems and methods are provided. In one embodiment, a method of dispensing a substance to an intended user is provided. The method comprises receiving an input from a biometric sensor; determining, based on the received input, whether an intended user's unique biometric attribute is detected by the biometric sensor; receiving an input from an environmental sensor; determining, based on the received input, whether a mouthpiece is positioned within a user's mouth; receiving an input from a capacitive sensor array of the mouthpiece; determining, based on the received input, whether an intended user's unique dentition is positioned within a recess of the mouthpiece; and dispensing a substance from a reservoir to a mouth of the intended user in response to determining that the intended user's unique biometric attribute is detected by the biometric sensor.