A multi-channel front-end for electrochemical sensing is presented. It consists of a multiplexed four-channel readout interface supporting amperometric, voltammetric, and potentiometric measurements. The electronic interface is co-designed according to the target biomarker specifications, and exhibits excellent linearity in both current and voltage sensing. The sensing front-end is characterized with lactate, paracetamol, and lithium sensing, yielding sensitivity of 1.2 ± 0.3 μ A/mM, 69.6 ± 2 nA/μM, and 55.6 mV/decade, respectively. These performances are comparable with the ones obtained with a bulky commercial Autolab potentiostat. Moreover, the limit of detection achieved are of 37 ± 8 μM, 2.1 ± 1.22 μM, and 11 ± 3.5 μM, respectively, for the aforementioned sensors. These values are more than one order of magnitude lower than the relevant detection range. This successful characterization demonstrates the ability of the proposed system to monitor, in a broader sense, metabolites, drugs, and electrolytes. The programmability, versatility and portability of the front-end interface paves the way for a continuous monitoring of different families of biomarkers, suitable for advanced healthcare diagnosis and wearable physiology.