Background: Women with gestational diabetes mellitus (GDM) are more likely to develop metabolic syndrome (MS). However, the effectiveness of web-based health management in preventing women at high risk of GDM from developing MS has rarely been studied. Purpose: The aim of this study was to evaluate the longitudinal effects of nurse-led web-based health management on maternal anthropometric, metabolic measures, and neonatal outcomes. Methods: A randomized controlled trial was conducted from February 2017 to February 2018, in accordance with the Consolidated Standards of Reporting Trials guidelines. Data were collected from 112 pregnant women at high risk of GDM who had been screened from 984 potential participants in northern Taiwan. Participants were randomly assigned to the intervention group (n = 56) or the control group (n = 56). The intervention group received a 6- month nurse-led, web-based health management program as well as consultations conducted via the LINE mobile app. Anthropometric and metabolic measures were assessed at baseline (Time0, prior to 28 weeks of gestation), Time 1 (36–40 weeks of gestation), and Time 2 (6–12 weeks of postpartum). Maternal and neonatal outcomes were assessed at delivery. Clinical trial was registered. Results: Analysis using the general estimating equation models found that anthropometric and metabolic measures were significantly better in the intervention group than the control group and varied with time. At Time1, the levels of diastolic pressure (β=−4.981, p = .025) and triglyceride (TG; β = −33.69, p = .020) were significantly lower in the intervention group than the control group, and at Time 2, the incidence of MS in the intervention group was lower than that in the control group (w2 = 6.022, p = .014). The number of newborns with low birth weight in the intervention group was lower than that in the control group (w2 = 6.729, p = .012). Conclusion/Implications for Practice: This nurse-led, web-based health management was shown to be effective in improving MS outcomes and may play an important role and show feasible clinical value in changing the current pregnancy care model.