Sol–gel derived multi-component silica nanocomposites are widely accepted as materials in a host of medical applications including bioactive drug carriers. In this paper, both the effect of polydimethylsiloxane (PDMS) (20, 25, and 30wt.%) on nanometre-scale phase separation and the surface properties of sol–gel processed polydimethylsiloxane/calcium phosphate/silica (PDMS-modified CaP/SiO2) are reported. The evaporation-induced self-assembly (EISA) technique was used to prepare the solid films of multicomponent silica nanocomposites. Atomic force microscopy (AFM) in PeakForce quantitative nanomechanical mapping (PF-QNM) mode was used to examine the surface heterogeneity including morphology, surface roughness, adhesion and elasticity of the composites structure on the nanometre-scale. The resulting materials were nanoscopically phase separated, but macroscopically uniform. PF-QNM results revealed the presence of elastic domains of PDMS-rich nanophase and rigid domains belonging to bioactive silica-rich nanophases. The nanophase separation depends on the amount of PDMS. This effect was correlated with an increase in the adhesion force, mean roughness (Ra) and root mean square roughness (Rq) and a decrease in the Young’s modulus in the composites as a function of PDMS content. The statistical analyses of these results showed significant differences between nanocomposites with different amounts of PDMS. The best compatibility and the nanophase dispersion were observed for 20% of PDMS in the nanocomposite’s structure.