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This study aimed to elucidate the metabolomic signature associated with obesity and periodontitis during pregnancy in plasma and saliva biofluids. Ninety-eight pregnant women were divided into: with obesity and periodontitis (OP = 20), with obesity but without periodontitis (OWP = 27), with normal BMI but with periodontitis (NP = 21), with normal BMI and without periodontitis (NWP = 30). Saliva and plasma were analyzed by ¹H-NMR for metabolites identification. Partial Least Squares-Discriminant Analysis (PLS-DA), Sparse PLS-DA (sPLS-DA), and Variable Importance of Projection (VIP) were performed. ANOVA and Pearson’s correlation were applied (<i>p</i> < 0.05). Plasmatic analysis indicated the levels of glucose (<i>p</i> = 0.041) and phenylalanine (<i>p</i> = 0.015) were positively correlated with periodontal parameters and BMI, respectively. In saliva, periodontitis was mainly associated with high levels of acetic acid (<i>p</i> = 0.024), isovaleric acid, butyric acid, leucine, valine, isoleucine, and propionic acid (<i>p</i> < 0.001). High salivary concentrations of glycine (<i>p</i> = 0.015), succinic acid (<i>p</i> = 0.015), and lactate (<i>p</i> = 0.026) were associated with obesity. Saliva demonstrated a more elucidative difference than plasma, indicating the glucose-alanine cycle, alanine metabolism, valine, leucine and isoleucine degradation, glutamate metabolism, and Warburg effect as the main metabolic pathways.