This paper investigates the detection of defects in honeycomb sandwich structures, including honeycomb core collapse, adhesive-free areas, and inclusions beneath both aluminum alloy and carbon fiber skins. Employing shearography and the theory of elastic mechanics thin plate deformation, the study compares and analyzes the detection of these defects under negative pressure loading and speckle interference. A normalized out-of-plane displacement index is introduced to examine the correlation between displacement and negative pressure for various defect types. The results show that shearography can be effective at detecting the honeycomb core collapse defects and adhesive-free defects with diameter greater than 10 mm, while it is not good at detecting the inclusion defects with diameter less than 20 mm. Under the same skin, the normalized out-of-plane displacement of honeycomb core defects is 2~5 times that of adhesive defects. This study can provide technical support for the detection and identification of defect types in honeycomb sandwich structures.