This report describes an open-air, screen-printed organic electrochemical transistor (OECT) fabricated on a paper substrate for the determination of halide ion concentrations within ranges relevant for human disease diagnosis. Chloride ions (Cl−) owing to their prevalence in biochemistry were specifically evaluated and the OECT’s efficacy with regards to measuring biologically relevant Cl− concentrations in the presence of multiple cationic and anionic interference species was studied. Sensor response was evaluated using both bench-top measurements as well as with hybrid data processing and notification circuitry assembled on the same flexible paper substrate as the OECT. To simplify the measurement process, a current-to-voltage converter was screen-printed in series with the OECT channel to facilitate voltage measurements in direct correlation with the drain current modulations. The bio-electronic conductive polymer poly(3,4-ethylenedioxythiophene) poly(styrene sulphonate) (PEDOT:PSS) was utilized as the transistor channel and silver (Ag) was used as the halide-selective gate electrode. Finally, the paper OECT and the on-board hybrid circuitry were powered using Zn-MnO2-ZnCl2 based printed paper cells and the biosensor’s suitability towards distinguishing between Cl− concentrations clinically associated with a diagnosis of cystic fibrosis was evaluated as a proof of concept. This work demonstrates a simple biosensing system working in the faradaic mode of operation without the implementation of selective ionophore films and incorporates aspects of recyclability, biodegradability and eco-friendliness.