Objective: Accurately capturing signals from healthcare devices worn on the body is vital for health monitoring, a field of growing interest. A flexible polyvinylidene fluoride (PVDF)-based piezoelectric sensor has been chosen for wearable applications. This study aims to optimize PVDF sensor performance by focusing on structural design. Methods: According to piezoelectric theory, this paper presents a mathematical expression system centered on the first-order piezoelectric equation, which describes the relationship between the electric displacement, the quantity of charge, and the output voltage of the PVDF film under strain. The study focuses on the features of weak physiological signals in the human body to establish a multi-layer shell structure finite element model using COMSOL Multiphysics. The analysis covers the electric displacement field mode, output charge, electric potential, and uniformity of stress distribution. We systematically investigated the impact of PVDF piezoelectric layer area, shape, thickness, and encapsulation materials on sensor performance using the controlled variable method. Results: As the area increases, the sensitivity and stress uniformity improve. Rectangular shapes exhibit more uniform stress distribution than circular shapes, and raising the aspect ratio within a certain range further enhances stress uniformity while maintaining comparable sensitivity. Increasing the thickness of the piezoelectric layer raises the electrical potential. Flexible encapsulation materials can provide higher sensitivity than rigid materials but are more susceptible to stress concentration. Conclusion: This paper finds the best structural form and parameter adjustment range of the PVDF sensor, which can provide a theoretical basis and numerical references for designing high-performance wearable sensors.