Background: The prevalence of pre-diabetes has been increased rapidly not in developing countries only. Pre-diabetes is associated with overweight. The diagnosis criteria of pre-diabetes are controversial issue. Aim of the work: The aim of this study was to establish useful parameters to predict pre-diabetes in overweigh adults. Subject and Methods: Thirty-eight adult participants were enrolled and they were divided into two groups 22 were control healthy volunteers and 16 participants were overweight. Biochemical investigations (glucose level, lipid profile), and High-molecular weight adiponectin (HMW-Adipo) hormone were done for both groups. Results: The results showed that the level of HMW-Adipo was significantly reduced in the overweight group, associated with an increase in fasting plasma glucose (FPG), triglycerides, and reduction in high-density lipoprotein (HDL-C) in the overweight group. The Pearson correlation for Triglyceride glucose- Body Mass Index (TyG-BMI), Body Mass Index (BMI), and tri-Ponderal index were positively correlated with FPG; while HMW-Adipo was negatively correlated with FPG. The area under the curve for TyG-BMI, PI and HMW-Adipo showed an excellent prediction for pre-diabetes in overweight adults. Conclusion: HMW-Adipo and/or TyG-BMI are better predictive markers for pre-diabetes adults rather than TyG-index and impair fasting glucose alone.