Next generation body-machine interfaces are attractive for both healthcare applications and consumer products. However, interfacing with biology requires electronic hardware with 1) excellent mechanical compliance, 2) operational stability in physiological environments, 3) reliable harnessing, discerning, amplification, and transduction of physiological information, and 4) ability to adapt or learn from physiological surroundings and execute tasks accordingly. For this highly demanding task, iono-electronics, where a semiconductor responds to incoming ions and undergoes a property change (electronic, optical, mechanical) which is in turn detected or utilized for a specific application are promising candidates. Though conjugated polymers have shown to be ideal conductors for such applications, only a few mixed conductors are studied to date and a one-material-fits-all bottleneck continues to hamper rapid advancements. The challenge lies in the lack of a cross-disciplinary design approach of high-performance materials. Establishing the needed balance between the two antagonistic modes of transport (ion permeability and electronic charge transport) to yield high performance devices has not only become an exciting field of fundamental research, but also a conduit towards advanced electronics. My lab at MIT (the laboratory of organic materials for smart electronics, OMSE Lab) employs molecular design to meet performance requirements in polymer-based iono-electronics. In this talk, I will share our ongoing efforts in designing novel semiconductors with varying degrees of ion-responsiveness and the scope of applications enabled by molecular tuning. We utilize copolymerization as a facile route to yield a library of mixed conductors enabling a variety of applications ranging from rapidly switching electrochemical transistors to high-fidelity artificial synapses. We have shown that by systematically tethering polar side groups onto known excellent electron conductors, we can probe the contribution from both ionic and electronic conduction to the resulting device performance and determine suitable applications. Lastly, my talk will introduce how we are utilizing these novel conductors to design redox-active nanocomposites combining biocompatibility, electrochemical sensing, and neuromorphic signal processing towards high performance bio-probes.