Abstract Background Labor migration is a challenge for the globalised world due to its long-term effects such as the formation of transnational families with the particularly vulnerable groups of left-behind children (LBC). These families, where family members of migrant workers are 'left-behind' are becoming common practice in many developing countries. In this systematic literature review, we aimed to investigate the impacts of parental labor migration on the mental health and well-being of their LBC. Methods Following the PRISMA guidelines, we performed a systematic literature search in English using PubMed, PsychINFO, Web of Science, Cochrane Library and Google Scholar for studies, investigating mental health and well-being among LBC who live in transnational families. Case-reports, qualitative studies as well as opinion papers were excluded. We summarized the evidence and additionally compared quantitative results. Results 25 studies were selected for the final analysis. We found that mental health and well-being outcomes of LBC differ across regions and sometimes even within regions. Only studies conducted in South America and South Asia observed purely negative effects. Overall, LBC show abnormal SDQ (Strengths and Difficulties Questionnaire) scores and report higher levels of depression and loneliness, than children who do not live in transnational families. Evidence suggests that gender of migrant parent, culture and other transnational family characteristics such as family arrangement, the role of the mother and the role of the father contribute to the well-being and psychological health of LBC. Conclusions International migration of parents has more negative than positive effects (e.g. through remittances) on the mental health and well-being of LBC. However, the effects strongly depend on family arrangements and care giving practices in migrants' sending countries. Key messages Further research utilizing longitudinal data is needed to better explore the complex and long-term effects of parental migration on LBC. Multidimensional family characteristics are crucial and should be better explored when examining the impacts of migratory separation on left-behind children.