The aim of this study was to evaluate the biofluid metabolome of kidney transplant recipients and their possible association with periodontitis. This was a cross-sectional, analytical, and descriptive study involving 61 patients, who visited the Dental School of Paulista University. Participants were arranged in four groups: GT: kidney transplant recipients without periodontal disease (n = 11); GTDP: kidney transplant recipients with periodontal disease (n = 12); CG: normal renal function without periodontal disease (n = 19); and GCDP: normal renal function with periodontal disease (n = 19). Saliva and urine samples were collected for further metabolomic analysis. The gas chromatography/mass spectrometry technique was used to evaluate the metabolites. The data obtained were analyzed using principal component analysis (PCA) to determine the main metabolites in the samples; Permanova was used to statistically compare the four groups using all metabolites simultaneously; the Jaccard similarity index was used to directly compare the similarity of the groups in terms of the presence of metabolites; and a Venn diagram, in which all salivary and urine metabolites were plotted, was used to evaluate the distribution of metabolites between groups. Statistica 12, SPSS 20, Past 3.0, Origin Pro 2019, and MetaboAnalys 5.0 statistical programs were used to obtain the results. The study identified 23 and 30 metabolites common to the GT and GTDP groups when the saliva and urine samples were analyzed, respectively; the benzene class and its derivatives were overexpressed. The most important metabolite for determining the pattern of PCA performed in saliva samples was ornithine and that in urine samples was palmitoleic acid. There was no significant difference between the salivary and urinary metabolites when compared among the four groups; however, it was possible to differentiate the specific metabolites for each group and the relationships between them. Metabolites shared in salivary samples of patients with periodontal disease are related to the fermentation process and bacterial metabolism, suggesting that they are potential indicators for periodontal injury.