Abstract <p>Fouling of ion-exchange polymeric membranes during operation is one of the problems that reduces the efficiency of devices based on them. Potentiometric membrane sensors are no exception. The approaches ensuring the long-term stability of their characteristics during the analysis of real media may be similar to those for protecting membranes in electrodialysis units. This work studies the electrode-active properties of homogeneous membranes based on a commercial copolymer of tetrafluoroethylene with sulfonated perfluorovinyl ether and novel grafted membranes based on a copolymer of polyvinylidene fluoride and sulfonated polystyrene in potentiometric sensors for the analysis of pharmaceuticals, artificial saliva solutions, and real samples of oral fluid. The patterns of change in the equilibrium and transport characteristics of the grafted membranes depending on the grafting degree and the conditions for polyaniline synthesis in them have been established. The results were compared with those for perfluorinated membranes. It was shown that polyaniline as a modifier of homogeneous and grafted sulfonated membranes increased their resistance to fouling due to its “cross-linking” effect on hydrophilic clusters and hydrophilization of the surface. The effect was achieved by suppressing the absorption of low-molecular-weight cations of drugs and metabolites with nitrogen-containing proton-acceptor groups, as well as the adsorption of high-molecular-weight components of physiological fluids.</p>