In this study, biocellulose (BC) membranes have been investigated as caffeine topical delivery systems, for the potential treatment of cellulite. BC-caffeine membranes were prepared by a simple approach and the permeation of caffeine through human epidermis, from BC or from conventional formulation systems (solution and gel), was compared in vitro to assess their therapeutic applicability. Diffusion studies with Franz cells showed that the incorporation of caffeine in BC membranes provided lower permeation rates than those obtained with the conventional formulations. These results combined with the possibility of producing BC membranes with different shapes demonstrate that these materials are promising biosystems for topical delivery of caffeine, showing reproducibility and an extended and predictable caffeine release over time, leading to their potential use for cellulite attenuation.