Flexible pressure sensors have attracted significant attention due to their wide range of applications in various fields (e.g., robotis, healthcare, and human–machine interfaces). However, achieving both high sensitivity and a wide detection range remains a challenge. Here, we propose a novel starfish-inspired ultrasensitive piezoresistive pressure sensor capable of detecting an extensive range of pressures. The sensor’s design incorporates high and low spine structures inspired by the surface of a starfish, efficiently preventing rapid saturation of detection range and expanding the response range. Unlike single-material nanofiber structures, the ultrathin and ultrasensitive layer, fabricated using PEDOT: PSS/TPU nanofibers, possesses a large surface area ratio and numerous contact points. This allows for a quick increase in conductive channels when pressure is applied. The intertwining of PEDOT: PSS fibers with TPU fibers enhances both the mechanical strength of the fiber membrane and the initial resistance of the sensor, thereby increasing its sensitivity. Additionally, PVA fibers are fabricated over the interdigital electrode to serve as insulation layer for controlling resistance change between the sensitive layer and the electrode. Importantly, the interaction between the PVA fibers and the PEDOT: PSS/TPU fibers alters the deformation behavior of the sensitive layer fibers, further enhancing the performance of the sensor. The fabricated sensor demonstrates exceptional sensitivity (302.9 kPa−1), an extensive detection range of 0–426.7 kPa, and remarkable endurance of over 7,000 cycles at 110 kPa, rendering it a device with great potential for precise pressure sensing applications in health monitoring and intelligent production.