Platelet dysfunction is increasingly recognized as a significant complication in individuals living with human immunodeficiency virus (HIV), with implications for disease progression, coagulopathy, and cardiovascular risk. While antiretroviral therapy (ART) has transformed the management of HIV by suppressing viral replication and restoring immune function, emerging evidence suggests potential risks associated with ART-induced platelet dysfunction. This review examines the multifaceted relationship between platelet dysfunction and HIV infection, with a focus on the potential risks associated with ART. We explore the pathophysiology of platelet dysfunction in HIV, the impact of ART on platelet function, and the clinical implications for HIV-infected individuals. Additionally, we discuss strategies for assessing and managing platelet dysfunction in the context of ART. Understanding the interplay between HIV infection, ART, and platelet dysfunction is crucial for optimizing patient care and minimizing treatment-related complications in HIV-infected individuals.