Integrated Microfluidic-Microelectronic Systems have recently received significant interest, as a new paradigm in the design and implementation of chemical/biological analysis platforms, for both clinical and research purposes. This paper presents a novel method for monitoring drug cytotoxicity using a hybrid microfluidic CMOS platform. This platform consists of an array of 8×8 capacitive sensors integrated with a readout circuit on the same chip. In this paper, we present a layer-by-layer (LBL) polyelectrolyte deposition process to coat the surface of microelectrodes realized in the top most metal layer in 0.35 μm CMOS process. This process can successfully enhance the biocompatibility of sensing microelectrodes and consequently increase the cell viability over a three-day period. Herein we demonstrate and discuss the advantages of proposed platform for drug cytotoxicity as well as cellular growth monitoring. This re-configurable, high throughput, cost-effective and low complexity sensing platform with a wide output dynamic range allows tracking of cellular activities such as cell growth at initial cell concentrations ranging from 10 to 200 KCells/ml. We also use standard Alamarblue cell-based assay and Geneticin selective antibiotic (G418) as control and cytotoxic drugs introduced to non-resistant H1299 and resistant Hek293 cell lines respectively. Furthermore, a low complexity microfluidic packaging technique is presented to create and bond micro-wells on CMOS chip for rapid test and characterization. With the potential to perform label free cellular analysis, the proposed platform opens an avenue to transit from traditional to smart cellular analysis techniques suitable for a variety of biological applications, in particular high throughput cell based drug testing.