This study examines changes in phenolic compounds and the antioxidant activity of Mexican mango seed in the bioprocess of solid-state fermentation (SSF) with the fungus Aspergillus niger GH1. The chemical composition and evaluation of mango seed as solid fermentation substrate support was also evaluated. Because of the chemical composition and the rapid growth of the fungus, mango seed is a suitable material to be used in SSF. The results showed that SSF of mango seed mobilized the polyphenolic compounds and improved the nutraceutical properties. The total phenol content in ethanol extract increased (p < 0.05) from 984 mg GAE/100 g to 3288 mg GAE/100 g at 20 h of fermentation. Total phenolic and HPLC-MS analysis of the free and bound fractions showed that SSF is an effective method to release the bound phenols, suggesting that this strategy may help to enhance potential antioxidant. Therefore, fermented mango seed extracts are particularly promising as natural antioxidants.