Flexible piezoresistive sensors hold great promise in biomedicine and personal motion detection, attracting significant attention from researchers. Particularly, two‐dimensional (2D) MXene has made remarkable strides in biomedicine, electromagnetic shielding, and other practical applications, due to its exceptional hydrophilicity, biocompatibility, mechanical properties, surface functional groups, and large specific surface area. The ease of composite material formation further makes it ideal for high‐sensitivity flexible sensors. This paper summarizes the principal structural configurations for the multi‐scale interfaces, performance assessment metrics, and the corresponding sensing mechanisms of flexible piezoresistive sensors. Subsequently, the main characteristics and synthesis methods of MXene, especially the related applications and parameters are introduced in detail. The research trends and typical applications of MXene‐based flexible piezoresistive sensors focused on film structures, fiber structures, 3D structures, and hydrogel structures, are highlighted systematically. In addition, the challenges and prospects that promoting the advancement of MXene‐based flexible piezoresistive sensors in future are also discussed, which will revolutionize the sensing field and offer a wealth of opportunities in biomedicine and beyond.