Paracetamol or acetaminophen is the main non-opioid analgesic recommended for mild pain by the World Health Organization (WHO) analgesic ladder. However, the high levels used of paracetamol are associated with the hepatotoxicity and nephrotoxicity caused by accumulation of toxic metabolites. The sensor is produced on a polyester substrate containing a full electrochemical device with working, auxiliary, and reference electrodes in which, guiding personalized medicine solutions are not reported. Temporal paracetamol profiles in human saliva are performed with the subject taking different amounts of commercial analgesic pills. The variation of saliva paracetamol levels is demonstrated to be interference free from electroactive interfering species and human saliva constituents. In addition, the sensor displays to be useful as a disposable device for the fast detection of paracetamol in untreated raw saliva following pill intake. The maximum concentration (C ) and half-life time (t ) for paracetamol are 143.27 µm and 110 min. The results demonstrate the potential of a simple strategy with electrochemical devices for noninvasive personalized therapy toward guiding drug interventions through tracking of active substance, detecting, and correcting insufficiency of absorption to meet individual needs avoiding overdoses, side effects, and intoxication.© 2023 Wiley-VCH GmbH.