Sexually-transmitted infections (STIs) are a global health concern worldwide as they cause acute diseases, infertility, and significant mortality. Among the bacterial, viral, and parasitic pathogens that can be sexually transmitted, human immunodeficiency virus (HIV) has caused one of the most important pandemic diseases, which is acquired immune deficiency syndrome (AIDS). 32.7 million people have died from AIDS-related illnesses since the start of the epidemic. Moreover, in 2019, 38 million people were living with HIV worldwide. The need to deal with this viral infection becomes more obvious, because it represents not only a problem for public health, but also a substantial economic problem. In this context, it is necessary to focus efforts on developing methods for prevention, detection and treatment of HIV infections that significantly reduce the number of newly infected people and provide a better quality of life for patients. For several decades, biomedical research has been developed allowing quick solutions through the contribution of effective tools. One of them is the use of polymers as vehicles, drug carrier agents, or as macromolecular prodrugs. Moreover, nanosystems (NSs) play an especially important role in the diagnosis, prevention, and therapy against HIV infection. The purpose of this work is to review recent research into diverse NSs as potential candidates for prevention and treatment of HIV infection. Firstly, this review highlights the advantages of using nanosized structures for these medical applications. Furthermore, we provide an overview of different types of NSs used for preventing or combating HIV infection. Then, we briefly evaluate the most recent developments associated with prevention and treatment alternatives. Additionally, the implications of using different NSs are also addressed.