The digestive stability of two natural antioxidant compounds present in virgin olive oil, hydroxytyrosol (HTy) and hydroxytyrosyl acetate (HTy-Ac) and a new series of hydroxytyrosyl ethers (methyl, ethyl and butyl hydroxytyrosyl ethers) was evaluated by a simulated digestion procedure. High recovery of all compounds after gastric digestion was obtained, although they showed a statistically significant lower stability after pancreatic-bile salts digestion. HTy-Ac was partially hydrolyzed into free HTy, whereas after intestinal digestion, HTy was converted into 3,4-dihydroxyphenyl acetic acid (DOPAC), and HTy-Ac was hydrolyzed to HTy and subsequently transformed into DOPAC. In contrast, no chemical modification of hydroxytyrosyl ethers during in vitro digestion was observed. In summary, HTy, HTy-Ac and hydroxytyrosyl ethers show high and interesting digestive stability and the new synthetic hydroxytyrosyl ethers showed enhanced chemical stability compared to HTy and HTy-Ac.