A sandwich panel with superior blast resistance was designed and fabricated by filling aluminum honeycomb cores with two shear thickening gels (STGs) of different compositions, SG and TG. A series of blast experiments were conducted to investigate its dynamic response. The digital image correlation (DIC) technique was used to record and analyze the experimental process, exploring the coupling mechanism between the STG filling and the honeycomb core and its effect on the dynamic behavior of the structure. In addition, by analyzing the deformation modes, strain histories, and failure patterns of the front and back face sheets as well as the core layer, the effects of honeycomb cell size and STG type on the blast resistance of the sandwich panel were determined. Experimental results showed that the unfilled honeycomb sandwich panel suffered severe damage to both face sheets, indicating poor protective performance. The STG filling significantly enhanced the blast resistance, and the TG-filled panel achieved better protection than the SG-filled panel due to its stronger shear thickening effect. When the honeycomb cell size was 4 mm, the front face sheet of the SG-filled panel fractured, whereas the TG-filled panel exhibited more uniform plastic indentation, and the back face sheet deflection was reduced by 61.0%. When the honeycomb cell size was 8 mm, the TG-filled panel achieved reductions of 5.6% (front panel) and 17.7% (back panel) in deflection compared to the SG-filled panel. The experimental results indicate that optimizing the type of STG and honeycomb structural parameters can effectively modulate the blast resistance of the sandwich panel.