Microalgae are promising plant-like food sources rich in proteins and bioactive compounds with nutraceutical potential. This research investigated the health-promoting effects of high pressure homogenisation (HPH)-treated microalgal suspensions (8% w/v) of Arthrospira and Nannochloropsis species. These microalgal suspensions were treated using HPH at 300 bar, 600 bar, and 900 bar for a single pass. To gain valuable information on the bioavailability of potentially bioactive compounds, gastrointestinal digests obtained after in vitro simulated human gastrointestinal digestion of HPH-treated microalgal suspensions were examined for total phenolics, pigments, and antioxidant activity. Furthermore, their bioprotective potential was evaluated on an oxidatively stressed (induced by hydrogen peroxide) Caco-2 cell culture model system. Results showed that increasing the homogenisation pressure resulted in increased chlorophyll a and carotenoids release for both Arthrospira and Nannochloropsis species. Nannochloropsis sp. experienced an improved phenolics yield with HPH but a similar positive impact of HPH was not observed for Arthrospira sp. probably because of its inherent high phenolic content. Similarly, only Nannochloropsis sp. suspensions showed higher antioxidant activity by FRAP assay at 900 bar treatment. HPH-treated gastrointestinal digests of Arthrospira sp. treated at 600 bar and 900 bar demonstrated cell recovery and viability on stressed Caco-2 cells. However, there was an insignificant bioprotective effect from the HPH-treated Nannochloropsis digests. In general, it appears that the ideal homogenizing pressures for Arthrospira and Nannochloropsis suspensions are 300 and 900 bar, respectively. Overall, this study shows the potential of HPH as an efficient tool to produce functional foods and ingredients, particularly from Arthrospira sp. suspensions.