Selenium (Se) is an essential trace mineral known for its role as an antioxidant in oxidation-reduction reactions. Due to deficiency in many parts of the world, development of new Se supplementation is increasing in popularity. The objective of this study was to examine the bioaccessiblity (BAC) and bioavailability (BA) from Se-rich algae using an in vitro digestion/Caco-2 cell model. Algal samples were grown in Se-rich media with varying concentrations of either selenite or selenate, then subjected to in vitro digestion. The centrifuged supernatent was applied on the Caco-2 cell monolayer for a 24-h treatment. BAC was tested based on the Se solubility post in vitro digestion and BA by induction of cellular glutathione peroxidase activity (GPx1) in a Se deficient Caco-2 cell model. Algal samples were compared to Se-salts, selenomethionine (SeMet) and Se-yeast commonly used in supplementation. Cells treated with algae grown in selenate had a mean GPx1 activity that was 15-62% (p<0.05) of the GPx1 activity relative to the cells with SeMet treatment. Cells treated with algae grown in selenite had a mean GPx1 activity that was 11-34% (p<0.05) of the GPx1 activity from SeMet treated cells. Additionally, the Se-yeast treated cells had 134% (p<0.05) GPx1 activity, selenate salt treated cells had 214% (p<0.05) GPx1 activity, and selenite salt treated cells had 126% (p<0.05) GPx1 activity of the SeMet treated cells. The results indicated that the Se-rich algae was not as effective as traditional Se supplementation in increasing GPx1 activity. However, the results provided valuable information to improve future Se BA of algae.