Perforation is the most common illness of the tympanic membrane (TM), which is commonly treated with surgical procedures. The success rate of the treatment could be improved by novel bioengineering approaches. In fact, a successful restoration of a damaged TM needs a supporting biomaterial or scaffold able to meet mechano-acoustic properties similar to those of the native TM, along with optimal biocompatibility. Traditionally, a large number of biological-based materials, including paper, silk, Gelfoam®, hyaluronic acid, collagen, and chitosan, have been used for TM repair. A novel biopolymer with promising features for tissue engineering applications is cellulose. It is a highly biocompatible, mechanically and chemically strong polysaccharide, abundant in the environment, with the ability to promote cellular growth and differentiation. Bacterial cellulose (BC), in particular, is produced by microorganisms as a nanofibrous three-dimensional structure of highly pure cellulose, which has thus become a popular graft material for wound healing due to a number of remarkable properties, such as water retention, elasticity, mechanical strength, thermal stability, and transparency. This review paper provides a comprehensive overview of the current experimental studies of BC, focusing on the application of BC patches in the treatment of TM perforations. In addition, computational approaches to model cellulose and TM are summarized, with the aim to synergize the available tools toward the best design and exploitation of BC patches and scaffolds for TM repair and regeneration.