Human papillomavirus (HPV) infection is the most prevalent sexually transmitted disease, and a primary cause of persistent infection leading to cervical cancer (CC). CC remains one of the most common malignancies among women worldwide, with approximately 660,000 new cases and 350,000 deaths annually. In Mexico, this cancer accounts for 13.9% of female deaths. Currently, no antiviral treatment exists for HPV infection. Available therapies for dysplasia and CC focus on the destruction or surgical removal of infected tissue using cytotoxic agents. While the prophylactic HPV vaccine effectively prevents new infections, it does not benefit the millions already infected, underscoring the urgent need for novel therapeutic strategies. This study aimed to identify potential antagonists for the interaction between the HPV16 E2 and E1 proteins through in silico screening. A virtual screening was performed targeting the TAD of the HPV16 E2 protein (PDB ID: 1DTO) using the Maybridge HitFinder™ small molecule library. Six molecules with the best binding energies were identified: 11419, 11829, 10756, 10708, 10632, and 10726. Among these, molecules 10756, 10708, 10632, and 10726 demonstrated promising potential as antagonists, interacting with Tyr19 and/or Glu39 residues. These findings highlight potent therapeutic candidates against HPV-related diseases.