Acoustic sensors are able to capture more incident energy if their acoustic impedance closely matches the acoustic impedance of the medium being probed, such as skin or wood. Controlling the acoustic impedance of polymers can be achieved by selecting materials with appropriate densities and stiffnesses as well as adding ceramic nanoparticles. This study follows a statistical methodology to examine the impact of polymer type and nanoparticle addition on the fabrication of acoustic sensors with desired acoustic impedances in the range of 1−2.2 MRayls. The proposed method using a design of experiments approach measures sensors with diaphragms of varying impedances when excited with acoustic vibrations traveling through wood, gelatin, and plastic. The sensor diaphragm is subsequently optimized for body sound monitoring, and the sensor's improved body sound coherence and airborne noise rejection are evaluated on an acoustic phantom in simulated noise environments and compared to electronic stethoscopes with onboard noise cancellation. The impedance-matched sensor demonstrates high sensitivity to body sounds, low sensitivity to airborne sound, a frequency response comparable to two state-of-the-art electronic stethoscopes, and the ability to capture lung and heart sounds from a real subject. Due to its small size, use of flexible materials, and rejection of airborne noise, the sensor provides an improved solution for wearable body sound monitoring, as well as sensing from other mediums with acoustic impedances in the range of 1−2.2 MRayls, such as water and wood.