An inertial sensor with stress isolation structure includes a substrate, a suspension bridge, a guard ring and an electromechanical conversion mechanism. The substrate has a housing trough and an annular wall surrounding the housing trough. The suspension bridge is located in the housing trough and connected to the annular wall. The guard ring is connected to the suspension bridge and suspended in the housing trough. The suspension bridge is located between the substrate and guard ring. The electromechanical conversion mechanism is connected to and surrounded by the guard ring. Through the guard ring, interferences of applied forces to the electromechanical conversion mechanism can be reduced, precision of the inertial sensor can be improved, and performance impact caused by succeeding element package process can also be reduced. Thus package, test and calibration processes can be simplified to lower production cost.