Poly(vinylidene fluoride) nanocomposites processed with different morphologies, such as porous and non-porous films and fibres, have been prepared with silica nanoparticles (SiNPs) of varying diameter (17, 100, 160 and 300 nm) which in turn have encapsulated perylenediimide (PDI), a fluorescent molecule. Structural, morphological, optical, thermal, and mechanical properties of the nanocomposites, with SiNP filler concentration up to 16 wt% were evaluated. Further, cytotoxicity and cell proliferation studies were performed. All SiNPs are negatively charged independently of the pH and more stable from pH 5 upwards. The SiNPs introduction within the polymer matrix increases the contact angle independently of the nanoparticle diameters and the smallest ones (17 nm) improve the PVDF Young modulus from 0.94 ± 0.04 GPa for the pristine polymer film to 1.05 ± 0.06 GPa. Varying filler diameter, physico-chemical, thermal and mechanical properties of the polymer matrix were not significantly affected. Finally, the SiNPs inclusion does not induce cytotoxicity in murine myoblasts (C2C12) after 72 h of contact and proliferation studies reveal that the prepared composites represent a suitable platform for tissue engineering applications, as they allow to combine the biocompatibility and piezoelectricity of the polymer with the possible functionalization and drug encapsulation and release of the SiNP.