Several studies have demonstrated that nuclear magnetic resonance (NMR) metabolic profiles can differentiate patients with caries from healthy individuals; however, these studies only identified individual metabolites. The present study aimed to identify a salivary metabolite biomarker panel for the diagnosis of early childhood caries (ECC). Saliva samples from children with and without caries were analyzed using NMR spectroscopy. Multivariate and univariate analyses were performed to identify the discriminating metabolites. Selected metabolites were further evaluated and used to detect ECC. The saliva samples of children with ECC were characterized based on the increased levels of formate, glycerophosphocholine, and lactate and reduced levels of alanine, glycine, isoleucine, lysine, proline, and tyrosine. The levels of these metabolites were significantly different from those in the control in the ECC subgroup according to caries severity and correlated with the number of decayed and filled teeth or surfaces. Subsequently, an optimal salivary metabolite biomarker panel comprising formate, lactate, proline, and glycine was developed. This panel exhibited a better diagnostic performance for ECC than a single metabolite. These results demonstrate that salivary metabolic signatures can reflect oral conditions associated with dental caries, thereby emphasizing the importance of distinct salivary metabolic profiles as potential biomarkers of ECC.