Investigation of new materials for biomedical applications has represented a relevant subject in the latest decade, enhancing versatile properties of lipids. It has been documented that the capabilities of lipid-based systems improve when they combine with polymers, proteins, and sugars. In this field, understanding the driving forces behind such hybrid systems is mandatory for biomedical applications. From this perspective, it is crucial to investigate the biophysical properties of this kind of material. Here, we investigate the biophysical properties of hybrid membranes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol, and octyl-beta-D-glucopyranoside (OGP). Lipid/sugar materials could have potential properties to use as nanovesicles for drug delivery. We encapsulate ibuprofen in lipid/sugar vesicles and evaluate their thermodynamics, hydrodynamics, and morphological properties by differential scanning calorimetry, dynamic light scattering, and scanning electron microscopy. We found that OGP combined with cholesterol modifies thermodynamic parameters of membranes such as phase transition temperature, enthalpy change, and cooperativity. Lipid vesicles containing OGP at 6.0 mM loaded with ibuprofen demonstrated good stability after 3 months of storage. Furthermore, electronic microscopy revealed the presence of well-defined liposomes. We conclude that cholesterol and OGP can act synergistically in polar-nonpolar spaces of the DPPC bilayer, where the hydrophobic nature of ibuprofen leads to incorporation into this hybrid core, which implies changes in the fluidity and compactness of the membrane occurring at temperatures of biological relevance. This investigation provides crucial knowledge regarding the biophysical properties of thermo-responsive biohybrid vesicles potentially to use in nanomedicine, which could be of practical reference for designing innovative drug delivery systems. [GRAPHICS]