This study sought to analyze the impact of Metabolic Syndrome (MeS) and Type 2 Diabetes (T2DM) on metabolism and their relationship of Body Mass Index (BMI) and to identify potential predictive protein biomarkers for MeS and T2DM. The proteomes of saliva and blood, clinical parameters were analyzed in 103 adult individuals from the State of Rio de Janeiro, Brazil, a mixed-race population. Healthy individuals were sorted by their Body Mass Index (BMI) in normal (n=29), overweight (n=25) and obese (n=15) and were compared with individuals with MeS (n=23) and T2DM (n=11). Random forest predictive model revealed that 3 clinical variables, BMI, HOMA-IR, and fasting blood glucose, are most important for predicting MeS and T2DM. A total of 6 plasmatic proteins (ABCD4, LDB1, PDZ, Podoplanin, Lipirin-alpha-3 and WRS) and 6 salivary proteins (Hemoglobin subunit beta, POTE ankyrin domain family member E, T cell receptor alpha variable 9-2, Lactotransferrin, Cystatin-S, Carbonic anhydrase 6), are enhanced in T2DM and in MeS. Salivary and plasmatic proteomes, in a population of brazil, demonstrates that the physiopathological conditions associated with abnormal weight gain, T2DM, and MeS share similar modifications in protein composition, offering potential predictive biomarkers, potentially mitigating the adverse health consequences of these metabolic disorders.