Although parents of sexual and gender minority (SGM) adolescents are key stakeholders in SGM adolescents using HIV pre-exposure prophylaxis (PrEP), there is limited understanding of parental concerns and attitudes about their SGM adolescents taking PrEP. Fifty-four parents in the West South Central region of the U.S. completed an online, mixed-method, cross-sectional questionnaire to explore their concerns and questions about PrEP. Quantitative and qualitative results show that participants were more concerned about side effects, drug interactions, (non)adherence, and eligibility and duration of PrEP. Parents are less worried about picking PrEP from a pharmacy or returning to follow-up lab testing every three months. Most parents reported receiving medication information their adolescent takes from a medical provider and the media. Findings from this study can inform the development of parent-based PrEP interventions. Without further parent-based research and programming, SGM adolescents may continue to be disproportionately affected by HIV.