A current challenge in materials science and biotechnology is to express a specific and controlled functionality on the large interfacial area of a nanostructured material to create smart biohybrid systems for targeted applications. Here, we report on a biohybrid system featuring poly(vinyl alcohol) as the supporting synthetic polymer and bovine serum albumin as the biofunctional element. The optimal processing conditions to produce these self-standing composite membranes are determined, and the composition and distribution of the bioactive agent within the polymeric matrices are analyzed. A post-processing cross-linking using glutaraldehyde enables this functional membrane to be used as a chemical filter in aqueous environments. By demonstrating that our mats can remove large amounts of ketoprofen from water, we show that the combination of a BSA-induced biofunctionality with a nanostructured fibrous material allows for the development of an efficient biohybrid filtering device for the large and widely used family of nonsteroidal anti-inflammatory drugs (NSAIDs). The crystal structure of the complex between BSA and ketoprofen is determined for the first time and confirms the interaction between the two species.