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. The structural, morphological, optical, thermal, and mechanical properties of the nanocomposites, with SiNP filler concentration up to 16 wt %, were evaluated. Furthermore, cytotoxicity and cell proliferation studies were performed. All SiNPs are negatively charged independently of the pH and more stable from pH 5 upwards. The introduction of SiNPs within the polymer matrix increases the contact angle independently of the nanoparticle diameter. Moreover, the smallest ones (17 nm) also improve the PVDF Young’s modulus. The 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 us to combine the biocompatibility and piezoelectricity of the polymer with the possible functionalization and drug encapsulation and release of the SiNP.