Durum wheat aleurone, thanks to its nutrient-rich composition, might be of potential use as a functional ingredient in cereal-based foods provided nutrients can be made available for absorption. We evaluated the in vitro bioaccessibility of thiamine, niacin, and phenolic acids in different aleurone fractions obtained with an industrial processing aimed to obtain material of different composition and particle size. Results indicate that the main phenolic compounds and vitamins investigated have a higher bioaccessibility when present in the inner part of the aleurone layer compared to the outer part of aleurone or the unfractionated bran. Moreover, an ultramicronization treatment employed to reduce particle size does not further improve the bioaccessibility of these compounds. We conclude that aleurone fractions from durum wheat bran could represent a nutritionally relevant ingredient, bringing together a high fiber content and an excellent bioaccessibility of vitamins and phytochemicals generally associated with nutritional benefits.