Novel freeze-dried porous composite scaffolds of silk fibroin-diopside were prepared from natural polymer of silk fibroin (SF) as a matrix and from diopside nanoceramic as a bioactive reinforcing agent through a modified freeze-drying method. Considering the superiority of both diopside and SF in terms of mechanical and biochemical properties (in comparison to similar ceramics and polymers, especially in maxillofacial specific applications), we investigated the effect of diopside nanoparticle contents in 20%, 30% and 40% nanocomposites of silk fibroin-diopside. In this study, we used silk fibroin and diopside by considering the biocompatibility and osteoconductivity of these in access materials, more importantly, their efficiency in maxillofacial bone regeneration, also their reproducibility and ease of fabricationMicrostructure studies illustrated that the bioactive diopside nanoparticles were distributed throughout the fibroin matrix. Enough porosity (at least 70% for 40% composite scaffolds), desired surface properties (excellent water uptake capacity and water contact angle), high mechanical strength (compressive module of 3.5 MPa and compressive strength of 0.39 MPa) and acceptable in vitro biocompatibility features (MC 3 T 3 preosteoblast cell attachment and growth) were achieved during the fabrication of the nanocomposite scaffolds without any extra hazardous modifications. it seems that the biocompatible diopside/SF nanocomposite can efficiently act as a peri-implant biomaterial in oral reconstruction surgeries and potentially can regenerate the new bone in defects of maxillofacial regions. It was hypothesized that embedding diopside nanoparticles within the walls of silk pores would enhance the mechanical properties and improve the wettability of silk fibroin matrix. Therefore, the effect of different amounts of diopside powders on the structure, strength and hydrophilicity of the fabricated composite scaffolds were examined. Keywords: Silk fibroin, Nanocomposite, Diopside, Bone tissue engineering scaffold