This paper reviews various design approaches for sensing schemes that utilize silicon nanowire (SiNW) ion-sensitive field-effect transistors (ISFETs) for pH-sensing applications. SiNW ISFETs offer advantageous characteristics, including a high surface-to-volume ratio, fast response time, and suitability for integration with complementary metal oxide semiconductor (CMOS) technology. This review focuses on SiNW ISFET-based biosensors in three key aspects: (1) major fabrication processes and device structures; (2) theoretical analysis of key performance parameters in readout circuits such as sensitivity, linearity, noise immunity, and output range in different system configurations; and (3) an overview of existing readout circuits with quantitative evaluations of N-type and P-type current-mirror-based circuits, highlighting their strengths and limitations. Finally, this paper proposes a modified N-type readout scheme integrating an operational amplifier with a negative feedback network to overcome the low sensitivity of conventional N-type circuits. This design enhances gain control, linearity, and noise immunity while maintaining stability. These advancements are expected to contribute to the advancement of the current state-of-the-art SiNW ISFET-based readout circuits.