Objective To determinate the recovery of total polyphenolic compounds content, in vitro antioxidant activity and HPLC/ESI/MS characterization of extract from Nephelium lappaceum L. (Mexican rambutan). Methods The rambutan husk extract was obtained by aqueous extraction and a polyphenolic fraction was recovered using Amberlite XAD-16. The total polyphenolic compounds content was determined by the Folin Ciocalteu and butanol-HCI methods. In vitro antioxidant activity was performed using ABTS and ferric reducing antioxidant power methods. Results Mexican rambutan husk showed a total polyphenolic content of 582 mg/g and an evident antioxidant activity by ABTS and ferric reducing antioxidant power analysis. The HPLC/ESI/MS assay allowed the identification of 13 compounds, most of which belong to ellagitannins. Geraniin, corilagin and ellagic acid were present in the sample; the mineral composition was also evaluated. Conclusions Rambutan husk cultivated in Mexico is a promising source for the recovery of added value bioactive compounds with antioxidant activity, which have potential applications as bioactive antioxidant agents for the treatment of diseases.