An electromechanical interface plays a pivotal role in determining the performance of a stretchable strain sensor. The intrinsic mechanical property of the elastomer substrate prevents the efficient modulation of the electromechanical interface, which limits the further evolution of a stretchable strain sensor. In this study, a chiral auxetic metamaterial (CAM) is incorporated into the elastomer substrate of a stretchable strain sensor to override the deformation behavior of the pristine device and regulate the device performance. The tunable isotropic Poisson's ratio (from 0.37 to -0.25) achieved by the combination of CAM and elastomer substrate endows the stretchable strain sensor with significantly enhanced sensitivity (53-fold improvement) and excellent omnidirectional sensing ability. The regulation mechanism associated with crack propagation on the deformed substrate is also revealed with finite element simulations and experiments. The demonstration of on-body monitoring of human physiological signals and a smart training assistant for trampoline gymnastics with the CAM-incorporated strain sensor further illustrates the benefits of omnidirectionally enhanced performance.