The present paper provides a detailed overview of surfactants' function in HIV/AIDS therapy, with a focus on medication administration, direct antiviral mechanisms, and microbicide formulations. The use of surfactant-based nanotechnology into antiretroviral therapy has resulted in the development of liposomes, polymeric micelles, nanoemulsions, and surfactant-modified biomaterials that provide controlled release and increased bioavailability of antiretrovirals. Furthermore, many surfactants have inherent antiviral activity, which disrupts the viral lipid envelope, inhibits viral replication, and prevents HIV from entering host cells. The paper also explores the potential of surfactant-based biosensors for HIV diagnostics, emphasizing their role in improving sensitivity and selectivity and recent progress in formulation design using surfactants such as sodium lauryl sulfate, poloxamers, and biosurfactants, emphasizing their safety, biocompatibility, and clinical potential. Key challenges including scalability, environmental impact, and user acceptability are discussed alongside emerging AI-driven approaches for personalized nanomedicine. Surfactant toxicity and limited biocompatibility remain key barriers. Developing safer, more effective surfactants is essential for future clinical progress.