Abstract Molecular-level mixed matrix membranes made of Matrimid ®/β-cyclodextrin (β-CD) sub-nanocomposites for dehydrating isopropanol by pervaporation have been fabricated and studied. The separation efficiency of such membranes containing ∼2 to 10 wt.% of β-CD is superior over the neat Matrimid ® membrane in terms of both flux and separation factor. However, phase separation due to β-CD agglomeration occurs with an increase in β-CD loading. Asymmetry in both morphology and surface property has also been observed. The separation properties depend upon the membrane mounting mode (i.e., using air-side or glass-side of the membrane against the feed during pervaporation tests). The flux and separation factor of both modes, nevertheless, display the same increase-and-decrease dependence on β-CD loading. The unique characteristics of β-CD such as hydrophilic exterior and interior cavity and the interactions between β-CD molecules and the polymer matrix may create additional interface channels for water diffusion and provide size discrimination and chain rigidification for water/isopropanol selection. As a result, compared to mixed matrix membranes incorporated MgO or zeolite nanoparticles, embedding a low percentage of β-CD into the Matrimid ® leads to the enhanced and superior separation efficiency. On the other hand, a higher loading of β-CD deteriorates separation performance due to the formation of a non-permeable β-CD network. The proposed Matrimid ®/β-CD mixed matrix materials may open new perspective for the development of mixed-matrix hollow-fiber membranes because of the sub-nano-sized β-CD and its unique molecular-level mixing characteristics.