The state space differential quadrature method (SSDQM) has been extensively used to obtain accurate semi-analytical solutions for static and dynamic response of layered composite structures. The analysis of layered panels with mixed boundary conditions through-the-thickness of edges has received very little attention. In this work, a general and flexible method to extend SSDQM for analysis of panels with mixed edge boundary conditions is introduced. A simplified mathematical condition is derived from the constraints inherent in SSDQM, to implement the mixed edge boundary conditions in a systematic manner. Considering the limited application of SSDQM to analyze panels with large thickness-to-length and interlayer stiffness ratios, the proposed approach is used to study bending and free vibration response of thick, soft-core sandwich panels with mixed edge conditions. Convergence studies and comparison with finite element solutions show that SSDQM based on the proposed approach provides rapid convergence and excellent accuracy.