In this work, we propose the use of complex, bioderived 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 the Pseudonitzchia multistriata diatom silica shell (the so called frustule), whose grating-like geometry provides large light coupling with external radiation, whereas its extruded, subwavelength lateral edge provides an 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 as a function of the metalization parameters and finally applied the nanostrucures for discriminating cell membrane Raman signals. In particular, we considered two cases where the membrane composition plays a fundamental role in the assessment of several pathologies, that is, red blood cells and B-leukemia REH cells.