Over the last decade, surface stress-based piezoresistive cantilever biosensors have been extensively explored as a potential alternative for conventional clinical diagnostic techniques. The design of piezoresistive cantilever sensors is a complex multi-variable problem which involves the interplay between the thermal, electrical and mechanical design aspects of their constituent materials and geometry. Even though the literature includes examples where researchers have devised designs of piezoresistive cantilever biosensors, a majority of them have focused primarily on improving the electrical sensitivity by either dimensional optimization or material changes of their constituent layers. However, there are two important aspects of the sensor design which have been seldom addressed: (i) the negative impact of the transverse section of the U-shaped piezoresistor on the electrical sensitivity, and (ii) thermal drift in the output characteristics of the sensor. Although a few researchers have focused on the aforementioned factors, they have analysed them independently without considering their interdependence and cumulative impact on the sensor performance. In this paper, we devise a dual material multi-part U-shaped piezoresistor comprised of two p-type single crystalline silicon longitudinal sections and a p-type polysilicon transverse section. Evaluation of the proposed piezoresistor is performed in two stages using a finite element method-based numerical tool. In the first stage, the performance of the sensor with the multi-part piezoresistor is compared with the reported piezoresistors available in the literature. In the second stage, a comprehensive investigation of the multi-part piezoresistor is carried out to maximize the sensor performance. Results show that, compared to a conventional U-shaped piezoresistor, the proposed piezoresistor achieves improvement in the sensitivity ratio by 8.12 times. © 2018 IOP Publishing Ltd.