The fruit of the date palm, Phoenix dactylifera L., is an essential raw material for a multitude of industries. The processing of date fruit results in the generation of a considerable quantity of seeds. Due to their abundance in high-added-value bioactive compounds, they have the potential to be exploited to make functional foods, food supplements, cosmetics, and pharmacology. The objective of this research was to assess the effect of in vitro digestion on the stability of the phytochemical composition and biological activities, as well as on the release of individual phenolics from date seed extracts of the Ourous cultivar. The total phenolic (TPC) and flavonoid (TFC) contents, the antioxidant capacity (ABTS, ORAC, FRAP, and DPPH), and the enzyme inhibitory potential against acetylcholinesterase, butyrylcholinesterase, tyrosinase (TYR), α-glucosidase (α-GLU), and α-amylase of extracts were evaluated before and after each digestion step (gastric and intestinal). Moreover, the release of individual phenolics, including phenolic acids and flavonoids, was quantified throughout the digestion process by UHPLC analysis. The results demonstrated a significant increase in both TPC (298 to 1042 mg GAE/g) and TFC (14 to 160 mg QE/g) after digestion. Furthermore, UHPLC analysis delineated an incremental release of individual phenolics, throughout the digestion process. In vitro digestion also enhanced the scavenging of ABTS (565 to 625 mg TE/g) and peroxyl (354 to 4580 mg TE/g in ORAC assay) radicals, as well as FRAP (978 to 1176 mg AAE/g), but resulted in a reduction in DPPH (578 to 249 mg TE/g) scavenging capacity. The enzyme inhibitory potential of the extracts decreased after digestion, although this was maintained or enhanced for α-GLU (87 to 86 %) and TYR (27 to 35 %), respectively. These findings indicate that the seed extract contains several bioaccessible components, which may enhance its functional attributes.