A great enhancement in Raman scattering (SERS) from heme-containing submembrane biomolecules inside intact erythrocytes and functional mitochondria is demonstrated for the first time using silver–silica beads prepared using a new method involving aerosol pyrolysis with aqueous diamminesilver(I) hydroxide as a unique source of plasmonic nanoparticles for SiO2 microspheres. The recorded SERS spectra reveal a set of characteristic peaks at 750, 1127, 1170, 1371, 1565, 1585 and 1638 cm−1, resulting from the normal group vibrations of the pyrrole rings, methine bridges and side radicals in the heme molecules. The SERS spectra of functional mitochondria are sensitive to the activity of the mitochondrial electron transport chain, thus making the method a novel label-free approach to monitor the redox state and conformation of cytochromes in their natural cell environment. The developed nanocomposites are highly suitable for the analysis of biological objects due to their robust synthesis and superior spatial and temporal signal reproducibility, which was preserved for a period of at least one year.