An opioid overdose rescue device is provided that includes an ingestible capsule. Within the ingestible capsule is a non-refillable drug dispenser comprising an opioid antidote and at least one sensor configured to detect at least one physiological parameter indicative of an opioid overdose. A controller is also contained within the ingestible capsule and is operatively coupled to the drug dispenser and the least one sensor. The controller is configured to receive a signal detected by the least one sensor of the at least one physiological parameter to actuate release of the opioid antidote from the drug dispenser into the intestine of the patient upon a determination that the at least one physiological parameter falls outside a threshold value or range for the at least one physiological parameter indicating that an opioid overdose has been detected.