The present work describes our studies of the influence of the electrostatic microenvironment on the observed oxidation–reduction potential of redox-labeled supramolecular bioconjugates. Our experimental results show that the charge of the protein (streptavidin), determined by the pH, strongly influences the redox potential of the incorporated ferrocene centers. This is due to the electrostatic contributions from the fixed charges in the protein that affect the relative stability of the redox species involved in the electroactive label. In addition, the ionic strength plays a central role in screening the stabilizing or repulsive interactions, thus further influencing the magnitude of the apparent redox potential. This dependence of the redox potential on pH and ionic strength was described in quantitative terms by following a similar approach to that previously used for interpreting the behaviour of electron transfer proteins. This work provides a framework to understand, rationalize and predict variations in redox potentials of electroactive centers incorporated into different soft matter-based complex environments, like supramolecular bio-architectures. The potential of the approach was demonstrated through creation of a pH-tunable bioelectrochemical interface with switchable behavior based entirely on redox-active supramolecular bioconjugates.