Commercial foam based piezoresistive sensors are promising flexible sensing units for wearable devices, while they suffer from relative low sensitivity, especially in low pressure range. Herein, inspired by scorpion slit organs, multi-scale closure piezoresistive sensors are developed by self-polymerization of a polydopamine (PDA) layer and a polypyrrole nanofibers (PPy NFs) layer on polyurethane (PU) foam, and constructing a macroscopic narrow orifice configuration (NOC), which allows the generation of a great mount of conductive paths at low pressure. The synergetic effects of inner space closure, pore collapse, and PPy NFs contact contributed to an ultra-high sensitivity of 0.8251 kPa−1, which surpasses reported foam-based sensors. The developed NOC foam possesses fast response time and recovery time (120 ms and 100 ms), high linearity, and excellent stability. Moreover, the sensor can be used to precisely detect the human walking, running, and jumping behaviors, and the grabbing force. When integrated into a sensing array, the NOC PPP foams demonstrated excellent potential to be used in human activity monitoring such as yoga postures and sleeping positions. This work provides new thoughts for designing biomimetic highly sensitive piezoresistive sensors and enhancing the foam stability using PPy NFs.