The purpose of this study was to investigate the loading properties of the non-psychoactive cannabidiol (CBD) in a new nanostructured lipid carrier (NLC), evaluating its bioaccessibility in gastric and intestinal simulated physiological media. CBD has a low water solubility, as well as high instability in simulated physiological conditions and in the acidic media, which results in a very low bioavailability—less than 6%. NLCs containing CBD (10 mg/mL), Compritol 888 ATO, Lauroglycol 90, Labrafil 2125, Tween 20, and Poloxamer 188 were formulated. This resulted in them being suitable for oral administration because the size was less than 200 nm, polydispersity index 0.152, and ζ-potential −39.21 ± 1.89 mV. Recovery and encapsulation efficiency were 100% and 93%, respectively. After two hours of incubation in simulated gastric fluid (SGF), NLCs remained unchanged, protecting CBD from acidic medium. Indeed, CBD is also reported to be not stable in media with pH = 7.4 at 37 °C, but our studies evidenced that in the presence of the intestinal fluid, the NLC was digested and formed an emulsion, which can protect and preserve the CBD chemical structure, as confirmed by the 100% recovery found after six hours. Accordingly, CBD-loaded NLCs are a promising oral formulation that optimize bioaccessibility in the small intestine.