Organic electrochemical transistors (OECTs) exhibit strong potential for various applications in bioelectronics, especially as miniaturized, point-of-care biosensors, because of their efficient transducing ability. To date, however, the majority of reported OECTs have relied on p-type (hole transporting) polymer mixed conductors, due to the limited number of n-type (electron transporting) materials suitable for operation in aqueous electrolytes, and the low performance of those which exist. It is shown that a simple solvent-engineering approach boosts the performance of OECTs comprising an n-type, naphthalenediimide-based copolymer in the channel. The addition of acetone, a rather bad solvent for the copolymer, in the chloroform-based polymer solution leads to a three-fold increase in OECT transconductance, as a result of the simultaneous increase in volumetric capacitance and electron mobility in the channel. The enhanced electrochemical activity of the polymer film allows high-performance glucose sensors with a detection limit of 10 × 10−6 m of glucose and a dynamic range of more than eight orders of magnitude. The approach proposed introduces a new tool for concurrently improving the conduction of ionic and electronic charge carriers in polymer mixed conductors, which can be utilized for a number of bioelectronic applications relying on efficient OECT operation.