Smartphone use, e.g., on social network sites or instant messaging, can impair well-being and is related to clinical phenomena, like depression. Digital detox interventions have been suggested as a solution to reduce negative impacts from smartphone use on outcomes like well-being or social relationships. Digital detox is defined as timeouts from using electronic devices (e.g., smartphones), either completely or for specific subsets of smartphone use. However, until now, it has been unclear whether digital detox interventions are effective at promoting a healthy way of life in the digital era. This systematic literature review aimed to answer the question of whether digital detox interventions are effective at improving outcomes like health and well-being, social relationships, self-control or performance. Systematic searches of seven databases were carried out according to PRISMA guidelines, and intervention studies were extracted that examined timeouts from smartphone use and/or smartphone-related use of social network sites and instant messaging. The review yielded k = 21 extracted studies (total N = 3,625 participants). The studies included interventions in the field, from which 12 were identified as randomized controlled trials. The results showed that the effects from digital detox interventions varied across studies on health and well-being, social relationships, self-control, or performance. For example, some studies found positive intervention effects, whereas others found no effect or even negative consequences for well-being. Reasons for these mixed findings are discussed. Research is needed to examine mechanisms of change to derive implications for the development of successful digital detox interventions.