###### Abstract  
Agricultural hemp (_Cannabis sativa_ L.) is currently underutilised for food and could be pivotal to the development and expansion of a low-carbon food production system and to contribute to sustainable diets. Dehulling hempeseed for food (for hempeseed hearts) generates several by-products, including hempeseed \"screenings\". This study assessed the effects of several bioprocessing treatments (using enzyme mixtures, yeast, and combinations of both) on hemp screenings nutrient and phytochemical content and their digestion and metabolism in vitro (using a gastrointestinal digestion model and incubations with human mixed microbiota-f faecal samples from three healthy donors). The nutrients and phytochemicals' metabolites were measured using targeted LC-MS/MS and GC analysis. The hempeseed screenings are rich in insoluble NSP (16.46 \(\pm\) 0.86%), protein (20.15 \(\pm\) 0.11%, with 3.83% tryptophan), syringaresinol, p-cumaric and protocatechuic acids. The hempeseed screenings are highly fermentable, resulting in a significant increase in acetic, propionic, and butyric acids following fermentation with faecal microbiota. The bioprocessing treatments significantly increased the extractability of the phytochemicals, especially in free and alkaline-labile forms, without improving the fibre fermentation. The findings from this study support the use of hempeseed screenings as a source of dietary nutrients for biodiversification and development of potential functional foods for metabolic and gut health. [[http://www.mdpi.com/journal/applsci](http://www.mdpi.com/journal/applsci)]([http://www.mdpi.com/journal/applsci](http://www.mdpi.com/journal/applsci))  
tetrahydrocannabinol (THC) and has immense industrial potential while being highly sustainable and environmentally beneficial [2]. Hempeseed has a high nutritional value containing 25 to 35% oil, 20 to 25% protein, 20 to 30% carbohydrates, 10 to 15% insoluble fibre [3; 4] and is rich in bioactive phytochemicals [5]. As high-protein crop, hemp could potentially rapidly meet the growing demand for plant protein and contribute towards meeting the \"Reference Nutrient Intake (RNI)\" (0.75 g protein per Kg body weight per day) [6]. Unlike soya and wheat protein, hemp is not currently defined as an allergen and hemp-based food products are not known to cause food allergies or coeliac syndrome [7]. As a source of dietary fibre, such as non-starch polysaccharides (NSP), could be fermented to short-chain fatty acids (SCFAs) by colonic microbes, impacting various physiological effects [8; 9]. The microbial-derived metabolites of protein (specifically aromatic amino acids) such as indole-3-propionic acid (IPA), associated with a lower likelihood of developing type 2 diabetes (T2D), the indoles recognized as possessing anti-oxidative and anti-inflammatory properties, and the 4-hydroxyphenylacetic acid (4-HPAA) being proposed for potential nutritional therapies for hepatic steatosis [10]. As these findings could be exploited to promote metabolic health and prevent chronic disease, it is, therefore, important to assess the bioavailability, metabolism, including fermentability, of high protein and fibre food crops such as hemp. The most studied hemp food by-product is the hemp meal produced after the oil extraction process and milled into flour to produce breads, potato chips, burger patties [11]. The consumption of hemp-rich meals (bread baked with hemp flour) beneficially modulated gastrointestinal hormones and promoted satiety in healthy individuals [12]. The dehulling of hempseeds to produce the hemp hearts removes the outer shell, mainly composed of fibre [4] and the hemp screenings, which are often discarded. Here, we have studied the \"hempseed screenings\" which are understudied hemp food by-products with the scope of developing potential functional food ingredients to promote zero-waste hemp food production and a circular nutrition and a circular economy.