Neuropeptide Y (NPY) biomarker levels have a close association with the diagnosis of Major Depression Disorder (MDD) and anxiety disorders. Quantifying NPY in correlation to self-reported symptoms will be an important measure to ensure a relatively uniform diagnosis and help with disease prognosis of these disorders. The work presented is a novel, passive eccrine sweat based, electrochemical detection platform for quantification of NPY biomarker levels. The paper offers a comparison between non-porous and porous sensor platforms using various electrochemical detection techniques. This work uses a novel strategy towards designing an optimal nanobioelectronic interface to measure NPY. The portability aspect of this detection platform is discussed by the demonstration a novel, portable EmStat Pico based electronic platform. The detection limit of the sensor is 10 pg mL⁻¹ and its range is 20–500 pg mL⁻¹. The NPY detection platform is envisioned to be a wearable point-of need monitoring system for management of chronic anxiety disorders and MDD.