Chronic or persistent human papillomavirus (HPV) infection is essential for the development of many types of carcinomas, such as cervical carcinoma. Developing new diagnostic and prognostic biomarkers and designing more effective targeted therapeutics and treatment strategies remains urgent. Numerous efforts have been made to design new drugs and vaccines to treat HPV infections. Due to the special HPV infection pathway, entry inhibitors to block viral entry into target cells have been extensively and deeply studied. This chapter reviews the basic characteristics of HPV infection and the various types of HPV entry inhibitors, which were found to have high safety, potent antiviral effects, and broad-spectrum activity against multiple HPV subtypes. Together with the use of prophylactic vaccines, the development and application of these entry inhibitors will reduce the incidence of HPV infection and associated cancers in the future.