Sandwich panel is a widely used protective component, this paper designs Bidirectionally Arranged Bionic sandwich Panel (BABP) and Unidirectionally Arranged Bionic sandwich Panel (UABP) according to the appendage of Odontodactylus scyllarus. Meanwhile, Triangular sandwich Panel (TP), Corrugated sandwich Panel (CP) and Elliptical arc sandwich Panel (EP) are accordingly designed as a comparison. Hyperworks and LS-DYNA are used to simulate the impact conditions, and the drop-weight test shows that the finite element simulation is reliable. Bionic sandwich panels have excellent protective effect at the impact velocity of 6–14m/s. UABP has the best comprehensive impact resistance by comparing the deformation, specific energy absorption (SEA) and peak force (PF) of the five kinds of sandwich panels under five impact velocities. Parameter analysis and response surface optimization work based on orthogonal experiments are carried out for UABP, the results are that the wall thickness T and the triangle-width ratio λ2 have extremely significant influences on the SEA, and the order of influence is T>λ2; the wall thickness T and the arc-width ratio λ1 have extremely influences on PF, and the triangle-width ratio λ2 has a significant influence on PF, and the order of influence is T>λ1>λ2. Both the errors about SEA and PF of the optimal solutions are less than 5%. The comprehensive evaluation index of the optimal UABP is larger than that of sandwich panels by 29.15%, 52.61%, 65.64%, 40.5%. This research is expected to provide new perspectives on the design of sandwich panels.