Background: As HIV/AIDS is considered a chronic disease; quality of life (QoL) has become an important focus for researchers and healthcare providers. Technology-mediated interventions have demonstrated improved clinical effectiveness in outcomes, such as viral suppression, for persons living with HIV/AIDS (PLWH). However, the evidence to support the impact of these interventions on QoL is lacking. Objectives: The aim of this paper was to assess the impact of technology-mediated interventions on QoL and to identify the instruments used to measure the QoL of PLWH. Methods: For this review we followed the PRISMA guidelines. A literature search was conducted in PubMed, CINAHL, Cochrane, and EMBASE databases in April 2016. Inclusion criteria limited articles to those with technology-mediated interventions as compared to usual care; articles with the population defined as HIV-infected patients; and articles with QoL measured as a health outcome in randomized controlled trials. The Cochrane Collaboration Risk of Bias Tool was used to assess study quality. Results: Of the 1,554 peer-reviewed articles returned in the searches, 10 met the inclusion criteria. This systematic review identified four types of technology-mediated interventions and two types of QoL instruments used to examine the impact of technology-mediated interventions on PLWH. Four studies of technology-mediated interventions resulted in improvement in QoL. Four studies considered QoL as a secondary outcome and resulted in a negative or neutral impact on QoL. Overall, four studies had a low risk of bias, one study had a moderate risk of bias, and the other five studies had a high risk of bias. Conclusions: The evidence to support the improvement of QoL using technology-mediated interventions is insufficient. This lack of research highlights the need for increased study of QoL as an outcome measure and the need for consistent measures to better understand the role of technology-mediated interventions in improving QoL for PLWH.