Abstract Background Malaria in pregnancy is one of the serious global problems of our time. There were wide concerns about IPT-DP versus IPT-SP for prevention of malaria during pregnancy. Objectives To assess the current latest evidence on the efficacy and safety of dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine for malaria in pregnancy. Search Strategy The Cochrane Library, EMBASE, PubMed and Web of science were searched from the earliest publication date available to July 4, 2019 Selection Criteria We included randomized controlled trials comparing dihydroartemisinin-piperaquine with sulfadoxine-pyrimethamine for malaria in pregnancy. Data Collection and Analysis Outcomes were analyzed using Risk ratios (RR) and 95% confidence intervals (CI). We did subgroup analysis about different intervals, including 4-6 or 8 weeks. Main Results A total of five studies with 4660 HIV-uninfected pregnant women in area of high malaria-transmission intensity were included in final synthesis. Meta-analysis showed dihydroartemisinin-piperaquine for intermittent preventive treatment resulted in lower rates of placental malaria (RR=0.50; 95%CI, 0.43–0.59) and infection with malaria parasites at delivery (RR=0.05; 95%CI, 0.01–0.24). In the subgroup analysis, dihydroartemisinin-piperaquine for intermittent preventive treatment at 4-6 weeks of administration was associated with a better effect for infection with malaria parasites at delivery. Conclusions Dihydroartemisinin-piperaquine was a promising alternative drug to sulfadoxine-pyrimethamine for intermittent preventive treatment in settings with high sulfadoxine-pyrimethamine resistance, especially at 4-6 weeks of administration. Based on real-world and other epidemiological settings, more data will be needed to identify the risk of adverse effects.