Background: Placenta-specific 1 (PLAC1) is specifically expressed in the placenta and plays a fundamental role in placenta function. Aberrant expression of PLAC1 has been reported in pregnancy-related disorders; however, its expression in gestational diabetes mellitus (GDM) has not been clearly elucidated. This study aimed to investigate the expression of PLAC1 in the placenta of GDM patients, and its relationship with clinical characteristics. Methods: This was a case-control study. Placental tissues were collected from 37 GDM patients (GDM group) and 38 pregnant women with normal glucose tolerance (control group), matched with respect to maternal age and gestational weeks. We examined the expression of PLAC1 in the placenta of both groups and determined its association with clinical indicators. The localization of PLAC1 was confirmed by immunohistochemistry analyses. Results: PLAC1 expression was significantly lower in the placenta of GDM patients. For the control group, PLAC1 was positively correlated with pre-pregnancy body mass index (BMI), BMI at delivery, the fasting insulin, triglyceride levels, and homeostasis model assessment during delivery. In the case of GDM patients, there was no correlation between PLAC1 and these indices. Additionally, PLAC1 protein was mainly expressed in the cytoplasm of syncytiotrophoblasts and chorionic stromal cells. Conclusions: The expression of PLAC1 was reduced in the GDM placenta, which provides insight into the pathophysiological changes occurring in the placenta of these patients.