Tympanic membrane (TM) is vulnerable to a variety of middle ear diseases. In some cases, reconstruction or repair of the TM is essential for recovering the hearing. Although there are many kinds of materials and therapeutics for TM reconstruction, tissue engineering of the TM is still in its initial steps of advancement. Treatment of damaged TM is usually carried out by otology-related techniques such as myringoplasty and tympanoplasty. Most of the novel tympanoplasty methods employ artificial grafts made of biomaterials and polymers for scaffolds. One biomaterial candidate for design and fabrication of synthetic grafts is spider silk, which has excellent mechanical and acoustic characteristics. On the other hand, the structural function of the spider web is also one of the potential inspirations for designing tissue-engineered grafts on micro-scale explorations. In this study, a bio-inspired design and analysis of silky TM grafts are carried out employing finite element modeling and vibro-acoustic investigation. A comparative and statistical analysis is also performed with experimentally validated data to check the suitability of the materials and design. The numerical study shows that the proposed bio-inspired models are appropriate for TM graft design and fabrication. The effects of inspired architecture and materials on obtaining an optimum design for TM grafts are put into evidence via a parametric study, and pertinent conclusions are outlined.