Objective: Gestational diabetes mellitus (GDM) is the most common metabolic complication during pregnancy. So, a large number of studies have evaluated the usefulness of different screening tests. The aim of this study was focused on the potential of only first-trimester screening used in the prediction of GDM. Materials and Methods: In this systematic review, we searched PubMed, EMBASE, and Scopus (between 2010 and 2020) and also searched the reference lists of the relevant articles manually. After performing a thorough evaluation of the 242 potentially eligible papers, only 60 papers were selected in terms of the inclusion criteria. Search key terms were combining „ Gestational diabetes‟ or „ GD‟ “ gestational diabetes mellitus” or” GDM” or pregnancyinduced diabetes‟ with at least one of the following terms: “ screening test” , “ first-trimester” , “ prediction” , “ marker predictor” , “ serum marker” . Results: A total of 161954 pregnant women were evaluated in these reviewed studies. Moreover, many tests were assessed in the first trimester of pregnancy to predict GDM. This review showed that hs-CRP, FPG, TG, and LDL-C along with maternal BMI in the first trimester were related to the increased risk of developing GDM. Other tests were used in only one or two studies. Conclusion: This review showed that hs-CRP, FPG, TG, and LDL-C along with maternal BMI in the first trimester were linked to an increased risk of developing GDM. It is recommended that further well-designed studies by considering the cost-effective advantages of these predictive tests, should be performed.