Genipap (Genipa americana L.) is a native fruit from Amazonia that contains bioactive compounds with a wide range of bioactivities. However, the response to genipap juice ingestion in the human exposome has never been studied. To identify biomarkers of genipap exposure, the untargeted metabolomics approach in human urine was applied. Urine samples from 16 healthy male volunteers, before and after drinking genipap juice, were analyzed by liquid chromatography-high-resolution mass spectrometry. XCMS package was used for data processing in the R environment and t-tests were applied on log-transformed and Pareto-scaled data to select the significant metabolites. The principal component analysis (PCA) score plots showed a clear distinction between experimental groups. Thirty-three metabolites were putatively annotated and the most discriminant were mainly related to the metabolic pathways of iridoids and phenolic derivatives. For the first time, the bioavailability of genipap iridoids after human consumption is reported. Dihydroxyhydrocinnamic acid, (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate, hydroxyhydrocinnamic acid, genipic acid, 12-demethylated-8-hydroxygenipinic acid, 3(7)-dehydrogenipinic acid, genipic acid glucuronide, nonate, and 3,4-dihydroxyphenylacetate may be considered biomarkers of genipap consumption. Human exposure to genipap reveals the production of derivative forms of bioactive compounds such as genipic and genipinic acid. These findings suggest that genipap consumption triggers effects on metabolic signatures.