The aim of this study has been to assess the composition and antioxidant activities of rice bran extracts submitted to a human simulated digestion, which extraction process was previously optimized. In order to adjust the optimum values for the extraction, D-optimal experimental design and response surface methodology have been applied. Phenolic compounds and γ-oryzanol contents have been used as response parameters. In this way, two different extracts have been obtained. The first one, was obtained with 100% water as solvent, and it was mainly composed by phenolic acids. Ferulic acid was the majority compound found with a concentration of 1.00 ± 0.03 mg/g extract, followed by p-coumaric acid (0.19 ± 0.02 mg/g), The second extract, extracted with ethanol as solvent, was a γ-oryzanol enriched fraction with a content of 14.41 ± 0.26 mg/g extract. The optimized rice bran extracts thus obtained were subjected to a process of human in-vitro digestion. In the first extract, with high polyphenol content, the phenolic content was oscillating during the digestion, like antioxidant activity. The oryzanol content found in this fraction (0.079 ± 0.002 mg/g) has not been detected in any phase of digestion. In the second extract, with a high oryzanol content at the beginning, oryzanol content was not detected in any of digestion steps. However, phenolic composition was stable in all phases of simulation (ranging from 0.117 and 0.094 mg/g in the case of ferulic acid). This fact evidence that oryzanol is not a bioavailability fraction, while phenolic compounds support to some extent, the conditions of digestion.