A physiological signal sensing structure, a stethoscope therewith, and a manufacturing method thereof are provided. The sensing structure for physiological signals includes a flexible substrate, a piezoelectric sensing structure and a damping structure. The piezoelectric sensing structure is disposed over the flexible substrate, and includes a first surface and a second surface. The second surface of the piezoelectric sensing structure faces the flexible substrate. The piezoelectric sensing structure is an arc with a curvature, and the first surface thereof may face outward. The damping structure may be disposed between the flexible substrate and the piezoelectric sensing structure. In an embodiment, a further amplifying structure is disposed over the first surface of the piezoelectric sensing structure and contacts or does not contact a top region of the first surface.