A Monolithic biosensing platform is presented for miniaturized amperometric electrochemical sensing in CMOS. The system consists of a fully-integrated current readout circuit for differential current measurement as well as on-die sensors developed by growing Platinum nano-structures (Pt-nanoS) on top of electrodes implemented with the top metal layer. The circuit is based on the switch-capacitor technique and includes pseudo-differential integrators for concurrent sampling of the differential sensor currents. The circuit further includes a differential to single converter and a programmable gain amplifier prior to an ADC. The system is fabricated in 0.35 μm technology and measures current within ±20 μA with minimum input-referred noise of 0.47 pA and consumes 9.3 mW from a 3.3 V supply. Differential sensing for nano-structured sensors is proposed to build highly-sensitive and offset-free sensors for metabolite detection. This is successfully tested for bio-nano-sensors for the measurement of glucose in sub-mili Molar concentrations with the proposed readout IC. The on-die electrodes are nanos- tructured and cyclic voltammetry run successfully through the readout IC to demonstrate detection of H₂O₂.