Organic mixed ionic-electronic conductors (OMIECs) have emerged as essential materials for applications in bioelectronics, neuromorphics, and energy storage, owing to their ability to transport both ions and electrons. While significant progress has been made in understanding their operation, the role of noncompensating ions in polymer redox processes remains underexplored, particularly in the context of their impact on charge compensation and device performance. In this study, we systematically investigate the influence of noncompensating ions on the performance of n-type OMIECs with and without polar side chains, focusing on their interactions with electrolytes containing anions from the Hofmeister series. Our findings reveal a stark contrast in charging behavior and organic electrochemical transistor (OECT) performance based on side-chain chemistry. Polar oligoether side chains promote interactions with anions, resulting in significant performance variations. We demonstrate the critical role of polymer side-chain interactions with the different anions, where polyatomic anions capable of infiltrating the film degrade device performance, particularly in terms of transconductance and operational stability. In contrast, OMIECs without side chains exhibit performance independent of the noncompensating ion nature. Through electrochemical analysis, spectroscopic techniques, and molecular dynamics simulations, we provide a comprehensive understanding of how ion incorporation and polymer–electrolyte interactions shape device behavior. This study highlights the transformative role of side-chain functionality in tailoring the properties of the OMIEC and offers a design framework for high-performance OECTs, enabling advancements in biosensing, neuromorphic computing, and beyond.