In contemporary bioanalysis, monitoring the antioxidant activity (AOA) of the human skin is used to assess stresses, nutrition, cosmetics, and certain skin diseases. Non-invasive methods for skin AOA monitoring have certain advantages over invasive methods, namely cost-effectiveness, lower labor intensity, reduced risk of infection, and obtaining results in the real-time mode. This study presents a new flexible potentiometric sensor system (FPSS) for non-invasive determination of the human skin AOA, which is based on flexible film electrodes (FFEs) and membrane containing a mediator ([Fe(CN)6]3–/4–). Low-cost available materials and scalable technologies were used for FFEs manufacturing. The indicator FFE was fabricated based on polyethylene terephthalate (PET) film and carbon veil (CV) by single-sided hot lamination. The reference FFE was fabricated based on PET film and silver paint by using screen printing, which was followed by the electrodeposition of precipitate containing a mixture of silver chloride and silver ferricyanide (SCSF). The three-electrode configuration of the FPSS, including two indicator FFEs (CV/PET) and one reference FFE (SCSF/Ag/PET), has been successfully used for measuring the skin AOA and evaluating the impact of phytocosmetic products. FPSS provides reproducible (RSD ≤ 7%) and accurate (recovery of antioxidants is almost 100%) results, which allows forecasting its broad applicability in human skin AOA monitoring as well as for evaluating the effectiveness of topically and orally applied antioxidants.