Noise, vibration, and harshness (NVH) are becoming crucial performances in electric vehicles (EVs), particularly an external wind noise. A high initial contact load of the door inner belt weatherstrip should be applied to prevent the wind noise from entering the interior of the vehicle. This in turn may cause a squeaking noise at the glass/weatherstrip interface. Thus, this study demonstrates a multidisciplinary design of the weatherstrip to simultaneously reduce the wind noise and squeak by designing thermoplastic vulcanizate (TPV) and friction material properties as well as the structural geometry of the weatherstrip. The minimum overlap value at the glass/weatherstrip was determined by considering the manufacturing deviation and deformation when the glass was stalled. The minimum contact load was measured experimentally at which the wind noise was kept constant. The compression set and damping properties of the TPV material were improved by 39% and 10%, respectively, by increasing the ethylene propylene diene monomer (EPDM) ratio and ethylidene norbornene (ENB) content. Moreover, flocking was applied on the surface of the weatherstrip which greatly reduced the squeaking noise by 89%. Furthermore, to predict the squeaking noise, friction-induced vibration was simulated using computer-aided engineering (CAE), and the CAD model was modified according to the design guide for reducing low noises. By evaluating vehicle level performances with the developed weatherstrip, simultaneous improvement in the wind noise (1.0–1.2 dB(A) reduction for the cabin and proximity noises) and squeaking noise (periodic noise in the frequency range of 0.1–1 kHz was disappeared) was found. This study can show enormous potential for the material and structural multidisciplinary design for NVH performances in next-generation vehicles such as autonomous EVs and urban air mobility.