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N-acylphosphatidylethanolamines (NAPEs), N-acylethanolamines (NAEs) and Endocannabinoids (ECs) are bioactive molecules that participate to the hedonic and homeostatic phenomena underpinning food intake. NAEs and ECs have a wide range of biochemical effects and derive from hydrolysis of NAPEs. NAEs and ECs are involved in different biological pathways since they are agonists of cannabinoid receptor-1 (CB1), transient receptor potential vanilloid 1 (TRPV1) and the peroxisome proliferator-activated receptor-α (PPAR-α). Moreover, NAEs are also able to link GPR119 which is expressed on cells in the small intestine, colon and stomach. The receptors are involved in food intake and in blood glucose control due to the regulation from the gastrointestinal tract (GIT) of GLP-1 secretion. Although NAPEs, NAEs and ECs are compounds widespread in nature, only few studies reported the amount of ECs and NAEs in some food products. The gut microbiota is able to control levels of ECs in both the gut and the adipose tissue in obese mice. In humans, a relationship between the changes in the gut microbiota and in the ECs system tone is not yet demonstrated. The studies described in this PhD thesis investigated the presence of NAPEs, NAEs and ECs in foods and tested their bioaccessibility in the oral cavity during food mastication in vivo and in the GIT in vitro to evaluate their potential availability to activate the receptors present on the alimentary canal mucosa. In the chapter 2 the concentration of NAPEs, NAEs and ECs in foods of different origin was assessed and the daily intakes upon a Mediterranean (MD), Vegetarian (VD) and Western diet (WD) were calculated. Data showed that NAPEs and NAEs were more abundant in vegetal than in animal food products. The estimated daily intake of NAPEs was in the order of hundreds milligrams with abundance being in MD=VD>WD. The intake of NAEs and ECs were in the order of hundreds or tens micrograms; the abundance of NAEs was in MD=VD>WD, while that of ECs was in MD=WD>VD. In the chapter 3 a sham feeding study was described. It showed the concentration of NAEs in stimulated saliva of healthy normal weight subjects. Interestingly, salivary concentration of NAEs increased upon food mastication compared to the mastication of a parafilm piece (stimulated saliva). The concentration of NAEs in the oral cavity within the first hours after food mastication was influenced by the type of dietary fiber (3% of β-glucan or whole-wheat bran) used for the preparation of biscuits. In the chapter 4 another sham feeding study was described. It aimed at evaluating the influence of individual nutritional status on bioaccessibility (release in saliva) of NAPEs and NAEs upon mastication of three biscuits differing for amount and type of fat. To this purpose three types of biscuits were prepared with 8% of extravirgin olive oil (EVOB), 8% of palm oil (PALMB) and without added fat (CONB). Data showed that the obese (OB) subjects had a higher release of NAPEs in unstimulated saliva than normal weight (NW) subjects, while the concentration of NAEs in both unstimulated saliva and stimulated saliva was higher in OB than in NW subjects. During the mastication of biscuits a higher concentration of salivary NAPEs and NAEs than a no food condition in both NW and OB subjects was found. In the chapter 5 the bioaccesibility of NAEs and ECs along the gastrointestinal tract in vitro using Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) simulating both physiological conditions and the microbial ecosystem found in the ascending (AC), transverse (TC) and descending (DC) colon was assessed. To this purpose we prepared two different diets: Mediterranean (MD) and Western diet (WD) and the supernatants deriving from the different phase of colon were analyzed by HRMS analysis to measure NAEs and ECs. Data showed that the diets did not influence the concentration of these compounds, but the microbiota composition could influence the release of compounds in the colon phase. Considering the results obtained from the experiments performed in this PhD thesis it is possible to conclude that: 1) NAPEs, NAEs and ECs are present in many food products at different concentrations. 2) In vivo studies showed that these compounds are released from food matrix during the mastication and that other food components (fibers and fats) as well as the individual nutritional status of individuals may influence both the delivery of these compounds from the food (bioaccessibility) as well as their persistence in the oral cavity after eating; this might influence liking of food and subsequent food intake. 3) During in vitro digestion with SHIME® the concentration of NAPEs, NAEs and ECs was hypothesized to be majorly influenced by the microbiota composition inside the system acting on the biosynthesis and degradation of NAEs and ECs arriving into the colon, independently from the diet. Specifically designed studies are necessary to elucidate better the influence of enzymatic activity of NAPE-PLD and FAAH at different sites of the alimentary canal and in the gut microbiota to ascertain the metabolic fate of dietary NAPEs, NAEs and ECS in vivo and to possibly find dietary strategy to modulate the concentration of these bioactive compounds at intestinal level.