Background After preterm birth, parents often conformed with difficulties such as negative emotions, lack of care knowledge and skills, and insufficient professional support. As a remote health guidance method, e-health can provide a series of support for premature infants and their parents during the transition period from neonatal intensive care unit (NICU) to home care. Objectives To determine the efficacy of e-health interventions in discharged preterm infants as well as their parents, and to describe the process outcomes and elements of these e-health interventions to inform the effective design of future interventions. Methods The systematic review of the randomized and non-randomized controlled trials on the follow-up effect of e-health on preterm infants and their parents discharged from NICU between the inception to May 2023 will be electronically searched in the following nine databases: Web of Science, CINAHL Complete (EBSCO), PubMed, Embase, the Cochrane Library, Ovid MEDLINE, China National Knowledge Infrastructure, WANFANG DATA, and SinoMed. Quality will be appraised, respectively, via the revised tool to assess risk of bias (RoB 2) and the tool for risk of bias in non-randomized studies of interventions (ROBINS-I). The main outcome indicators of preterm infants are breastfeeding rate, readmission rate, neurobehavioral development, and premature infant's body mass. The outcome indicators for parents of premature infants are anxiety, depression scale, and parenting competency scale. The RevMan 5.4 software provided by the Cochrane Collaboration will be used for statistical analysis of the data. Conclusion The results of this study may provide future development opportunities for e-health follow-up prevention in preterm infants and may support evidence-based decision-making for e-health interventions of post-discharge developmental support in preterm infants. PROSPERO registration number CRD42023410334.