ObjectiveTo systematically evaluate the changes in placental protein expressions in gestational diabetes mellitus (GDM) and their correlations with maternal insulin resistance (IR). Methods PubMed, Cochrane Library, Scopus, Web of Science, Embase, China National Knowledge Infrastructure, VIP database, Wanfang Database and CBMdisc were searched for case-control studies published from January 2009 to November 2021, which reported the placental protein expressions in GDM and their correlations with IR. Two researchers independently reviewed the literature, extracted data and evaluated the literature quality. RevMan 5.4 software was used for meta-analysis, and descriptive analysis was performed on data that cannot be combined. ResultsA total of 19 studies were included, comprising 2 012 patients. The results of meta-analysis showed that: the expression level of retinol binding protein 4 (RBP4) [standard mean difference=2.11, 95% confidence interval (CI) (1.64, 2.58), P<0.000 01] and the positive rate of protein tyrosine phosphatase-1B (PTP1B) [relative risk (RR)=1.56, 95%CI (1.29, 1.88), P<0.000 01] were up-regulated, and the positive rate of insulin receptor substrate 1 (IRS-1) [RR=0.69, 95%CI (0.60, 0.78), P<0.000 01] was down-regulated. The protein expression levels of RBP4 (P<0.000 01) and PTP1B (P<0.000 01) were positively correlated with homeostasis model assessment of insulin resistance (HOMA-IR), while the protein expression levels of IRS-1 (P<0.000 01) and APN (P=0.002) were negatively correlated with HOMA-IR, and glucose transporter 4 (GLUT 4) was not correlated with HOMA-IR (P=0.79). Descriptive analysis found that the expression levels or positive rates of adipocytokines (leptin, resistin), oxidative stress markers (xanthione oxidase, malondialdehyde, 8-isoprostaglandin),inflammatory factors (tumor necrosis factor α, Toll-like receptor 4, Galectin-3, Galectin-2, migration inhibitory factor),fetuin-A, forkhead box transcription factor 1, forkhead box transcription factor 3a and estrogen receptor α in GDM placenta were up-regulated and all were positively correlated with HOMA-IR. The expression levels or positive rates of insulin signaling pathway proteins [phosphoinositide 3-kinase (PI3K), protein kinases B (AKT), phospho-protein kinases B (p-AKT), GLUT 4] were down-regulated, PI3K and AKT were negatively correlatedwith HOMA-IR, while p-Akt had no correlation with HOMA-IR. ConclusionsThe dysregulation of placental protein expressions may mediate maternal IR exacerbation, thus promote the occurrence and development of GDM and other pregnancy complications. The causal relationship and regulatory mechanism are still unclear, which need to be further studied.