In order to fully utilize the energy absorption potential of hybrid structure composed of multiple materials, a variable thickness Carbon Fiber Reinforced Plastic/ aluminum (CFRP/Al) hybrid multi-cell tube is proposed, with a focus on the design strategies of variable thickness filament winding and multi-cell layout. First, based on the validated finite element (FE) model, a comparative study of different tube configurations is implemented to clarify the advantages and disadvantages of multi-cell hybrid tube. By analyzing the energy absorption contribution of two component materials and local structures, the bending instability mechanism of multi-cell hybrid tube at large angles is revealed to emphasize the necessity of variable thickness filament winding. It is found that multi-cell Al tube is the key factor to induce structural instability, and CFRP with positive gradient thickness distribution is beneficial to restrain the bending instability of hybrid multi-cell tube. Second, in order to better describe the influence mechanism of the design parameters, two comprehensive crashworthiness performance indicators for multi-angle compression conditions are proposed, namely comprehensive specific energy absorption and energy absorption stability. Then, a detailed parametric study is performed to explore the influence mechanism of the variable thickness winding parameters and multi-cell cross-section parameters on the comprehensive energy absorption capacity of the hybrid tube under multi-angle compression conditions. Finally, an application recommendation for the variable thickness CFRP/Al hybrid multi-cell tube is given to provide a reasonable design strategy. Furthermore, a comparative analysis of crashworthiness between the suggested CFRP/Al hybrid tube and reported typical energy-absorbing structures is carried out to reveal the superiority of the variable thickness CFRP/Al hybrid multi-cell tube in the energy absorption stability. This research provides valuable guidelines and suggestions for the crashworthiness design of multi-material hybrid structures facing complex loading conditions.