Organic semiconductors have demonstrated great ability to act as electroactive components at the interface with biological media, featuring in numerous bioelectronic applications over the past two decades. Electron-transporting (n-type) materials, in particular, are essential for probing biological events that involve generation of electrons such as metabolite sensing or for developing electrochemical complementary inverters. However, current n-type materials have a narrow scope and low performance compared to their p-type counterparts, providing ample opportunities for improvement through chemical design. This work explores the relationship between the structure of n-type polymers, their electrochemical activity and their performance in organic electrochemical transistors (OECTs) operating in aqueous electrolytes. The polymer series designed in this work consist of electron deficient units functionalised with polar ethylene glycol side chains, which ensure penetration and transport of hydrated ions into the bulk of the polymer. Using the widely investigated naphthalene diimide (NDI)-bithiophene motif, it was found that introduction of alkyl spacers in between the conjugated backbone and the ethylene glycol units improves the electronic mobility and operational stability of the polymer in OECTs. Next, the NDI core was laterally extended to enhance the polymer backbone coplanarity, with the aim of improving its charge transport properties. The naphthodithiophene diimide unit led to the development of polymers with improved stability during extended cycling relative to their NDI-based analogues, as well as stable n-type OECT operation in aqueous electrolytes. The third study employed a backbone engineering strategy to increase the electron affinity of isoindigo-based copolymers and allow n-type operation within the electrochemical window of water. The polarity of OECT operation was controlled through subtle backbone modifications, achieving a transition from unipolar p-type to unipolar n-type operation with a thickness-normalised gm of up to 60.10 and 0.148 S/cm, respectively.