Accurate and rapid detection of the causative agent of a disease is of great importance in controlling the spread of the disease. This work developed a biosensor with the Bi2Te3 family of topological insulators for detection of the SARS-CoV-2 virulence factor. The Bi2Te3 family is a three-dimensional topological insulator material with topologically protected surface states; the presence of these surface states facilitates charge transfer between the electrode and electrolyte interface. Compared with the detection performance of Bi2Se3, BiSbTeSe2, and a trivial insulator like Sb2Se3, Bi2Te3 exhibits superior characteristics. A Bi2Te3 electrochemical detection platform is utilized to fabricate a sensor that can detect SARS-CoV-2 DNA, RNA, and antigen for label-free target detection. The concentration range of DNA detection by the biosensor using Bi2Te3 is between 1.0 × 10-15 and 1.0 × 10-10 M, and the detection limit can reach 1.41 × 10-16 M. Furthermore, it exhibits excellent selectivity and maintains good stability even after being stored for 14 days. This study provides a new way to apply topological insulator materials in the field of biosensors and use their unique electronic structure to improve the accuracy and speed of disease detection and diagnosis.