Oral delivery of the protein drug insulin is not currently possible due to rapid degradation of the sec-ondary structure in low pH conditions in the stomach and under the influence of digestive enzymes in the gastrointestinal tract. Effective oral delivery of insulin and other protein-or peptide-based drugs will, therefore, require encapsulation in a material or nanoparticle. Herein we investigate the ability of the lipid bicontinuous cubic phase formed by two lipids, monoolein (MO) and phytantriol (PT), to protect encapsulated insulin from degradation by the enzyme chymotrypsin, typically found in the small intes-tine. High encapsulation efficiency (>80%) was achieved in both lipid cubic phases with retention of the underlying cubic nanostructure. Release of insulin from the cubic matrix was shown to be diffusion-controlled; the release rate was dependent on the cubic nanostructure and consistent with measured dif-fusion coefficients for encapsulated insulin. Encapsulation was shown to significantly retard enzymatic degradation relative to that in water, with the protective effect lasting up to 2 h, exemplifying the poten-tial of these materials to protect the encapsulated protein payload during oral delivery. (c) 2021 Elsevier Inc. All rights reserved.