In this work, we propose the use of complex, bio-derived nanostructures as efficient surface-enhanced Raman scattering (SERS) substrates for chemical analysis of cellular membranes. These structures were directly obtained from a suitable gold metalization of Pseudonitzchia multistriata diatom silica shell (the so called frustule), whose grating-like geometry provides large light coupling with external radiation, whereas its extruded, sub-wavelength lateral edge provides excellent interaction with cells without steric hindrance. We carried out numerical simulations and experimental characterizations of the supported plasmonic resonances and optical near-field amplification. We thoroughly evaluated the SERS substrate enhancement factor (EF) as a function of the metalization parameters, and finally applied the nanostrucures for discriminating cell membrane Raman signals. In …