Abstract: Ultra Wide Band (UWB) wireless communication technology works in a frequency band range of 3.1-10.6 GHz, which overlaps with the existing narrow system frequency band and easily causes inter-signal interference. In view of this, this paper proposes a method based on topological optimization to achieve notch design of UWB microstrip antennas in three specific frequency bands through the co-simulation of Matlab and HFSS. Using FR4 of 30 mm×40 mm×1mm as the dielectric substrate, the antenna configuration is designed by combining topology optimization and Gray Wolf Optimizer (GWO). The optimized configuration has a working bandwidth of 3.1-10.6 GHz, and a reflection coefficient S11>-10 dB in 3.1-3.76 GHz, 4.52-4.76 GHz and 7.12-8.27 GHz, which achieves 80% of the band resistance characteristics in the target band and effectively inhibits signal interference with WiMAX (World Interoperability for Microwave Access) and C band. The numerical example shows that the topology optimization method can be used to design multi-notched UWB microstrip antennas, which verifies the efficiency of the topology optimization method in the design of multi-notched UWB antennas, and expands the application of the topology optimization method in the field of antenna design.