In order to meet the stringent requirements for structural stability and precision in space-based gravitational-wave detection telescopes, a combined approach of 3D finite element modeling, modal analysis, random vibration analysis, and topology optimization based on the variable density method was used to investigate the lightweight design and performance enhancement of the telescope’s main support structure. The results show that the optimized configuration achieved a 10.7% reduction in mass while significantly improving structural stability and material utilization efficiency, with both modal frequencies and stress levels meeting design specifications. Additionally, vibration displacement and acceleration responses at the secondary mirror position were effectively suppressed. It is concluded that the integrated topology-size optimization design provides an effective solution for balancing lightweight requirements with structural rigidity, offering valuable insights for future spaceborne telescope structural design.