AbstractHemp (Cannabis sativa L.) seeds are considered a nutritional powerhouse, rich in proteins and unsaturated fatty acids. The market for hemp seed food products is growing, due to the loosening of constraints in industrial cultivation. During the food processing chain, the external part of the seed is discarded, although it contains a significant amount of proteins. Converting this material into value-added products with a biorefinery approach could meet the ever-increasing need for sustainable protein sources while reducing food waste. In this study, creating value from hemp byproducts was pursued with three different approaches: (i) chemical extraction followed by enzymatic digestion, (ii) liquid fermentation by strains of Lactobacillus spp., and (iii) solid-state fermentation by Pleurotus ostreatus. The resulting products exhibited a range of in vitro antioxidant and antihypertensive activity, depending on the proteases used for enzymatic digestion, the bacterial strain, and the length of time of the two fermentation processes. These byproducts could be exploited as functional ingredients in the food, pharmaceutical, and cosmetic industries; the suggested biorefinery processes thus represent potential solutions for the development of other protein-containing byproducts or wastes.