The aim of this study is to evaluate the diagnostic accuracy of the Metabolic Score for Insulin Resistance (METS-IR), Body Mass Index (BMI), insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), Waist-TG Index (WTI), and Lipid Accumulation Product (LAP), among Saudi women, determining gestational diabetes mellitus (GDM). This multi-center case-control study included 495 pregnant women from Saudi, comprising 145 with GDM, considering a mean age of 30.1±5.6 years, including 350 without GDM, with a mean age of 28.6±5.2 years. Anthropometric measurements and fasting blood samples were taken to assess glycemic and lipid profiles. The METS-IR and additional indices were computed. Diagnostic validity was assessed through the area under the curve (AUC) analysis. METS-IR showed the highest AUC of 0.66, signifying its superior predictive capability for GDM, with a sensitivity of 51.3% and specificity of 73.1%. BMI and LAP exhibited moderate predictive power, evidenced by AUC values of 0.63. Insulin and HOMA-IR demonstrated high sensitivity and lower specificity, indicating their effectiveness in early screening while also revealing their limitations as independent diagnostic instruments. WTI exhibited a moderate level of predictive capability, evidenced by an AUC of 0.61. In conclusion, METS-IR demonstrates promise as a tool for predicting GDM, exhibiting a favorable balance of sensitivity and specificity, which indicates its potential for incorporation into clinical screening protocols. The diagnostic accuracy of BMI, insulin, and other indices is enhanced when integrated with METS-IR. The research highlights the necessity for a thorough assessment strategy that integrates the clustering of metabolic indices to improve risk stratification and management of GDM, thereby minimizing negative outcomes for both mothers and infants. Subsequent investigations should focus on validating these results across varied populations and examining the long-term impacts on the health of the mother and fetus.