BACKGROUND: Smartphones play a critical role in increasing human-machine interactions, with many advantages. However, the growing popularity of smartphone use has led to smartphone overuse and addiction. This review aims to systematically investigate the impact of smartphone addiction on health outcomes. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to carry out the systematic review. Five electronic databases including Medline, Web of Science, PsycINFO, PubMed, and Scopus were searched to identify eligible studies. Eligible studies were screened against predetermined inclusion criteria and data were extracted according to the review questions. This review is registered in PROSPERO (CRD42020181404). The quality of the articles was assessed using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: A total of 27 of 2550 articles met the inclusion criteria. All of the studies were cross-sectional and focused on physical, mental, and neurological health outcomes. The majority of the studies focused on mental health outcomes and consistent associations were observed between smartphone addiction and several mental health outcomes. Anxiety and depression were commonly found to mediate mental health problems. A wide range of physical health sequelae was also associated with smartphone addiction. Furthermore, there was an association between smartphone addiction and neurological disorders. CONCLUSIONS: Our findings suggest that there are consistent associations between smartphone addiction and physical and mental health, especially mental health. Social awareness campaigns about smartphone addiction and its impact on physical and mental health are needed. Further studies, especially randomized controlled trials, are warranted to validate the impacts of smartphone addiction.