Osteoarthritis is a degenerative joint disease characterized by the progressive deterioration of articular cartilage, synovial inflammation and changes in periarticular and subchondral bone, being a leading cause of disability. Conventional treatments present several side effects and can involve the use of painkillers and non-steroidal anti-inflammatory drugs. In this sense, researchers have shifted the focus of new therapeutics to biomolecular agents and/or their combination with cells. However, the efficacy of these molecules is dependent on their metabolization which can differ according to the administration route and delivery approach. Consequently, tissue engineering strategy comprising the use of biomaterials can provide support for neo-tissue osteochondral repair/regeneration whilst conferring proper mechanical and functional features as well as protecting biomolecular agents from premature degradation. The current strategies and challenges used in biomaterials functionalization with peptides that can mimic ECM proteins or other natural soluble biomolecules, important to induce the complex interactions between cells and the ECM, are discussed herein. Many opportunities for treating OA are being explored by means of peptide-biofunctionalization of biomaterials which can be designed to be recognizable, induce differentiation, prevent infection, degrade at an intended rate or act as drug delivery systems for controlled release or even as simple triggers of cell behavior.