<p>Avoiding
faradaic side reactions during the operation of electrochemical devices is
important to enhance the device stability, to achieve low power consumption,
and to prevent the formation of reactive side‑products. This is particularly
important for bioelectronic devices which are designed to operate in biological
systems. While redox‑active materials based on conducting and semiconducting
polymers represent an exciting class of materials for bioelectronic devices,
they are susceptible to electrochemical side‑reactions with molecular oxygen
during device operation. We show that this electrochemical side reaction yields
hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), a reactive side‑product, which may
be harmful to the local biological environment and may also accelerate device
degradation. We report a design strategy for the development of redox-active
organic semiconductors based on donor-acceptor copolymers that prevent the formation
of H<sub>2</sub>O<sub>2</sub> during device operation. This study elucidates
the previously overlooked side-reactions between redox-active conjugated
polymers and molecular oxygen in electrochemical devices for bioelectronics,
which is critical for the operation of electrolyte‑gated devices in
application-relevant environments.</p>