The healing of osteochondral defects (OCD) resulting from injury, osteochondritis, or osteoarthritis in middle- and old-age individuals, bearing lesions in the cartilage and bone, pain, and loss of joint function, presents challenges to the clinical practitioners because of non-regenerative cartilage and the limitations of current therapies. Bioactive peptide-based osteochondral (OC) tissue regeneration is becoming more popular because it does not have the immunogenicity, misfolding, or denaturation problems associated with original proteins. Periodically, reviews are published on the regeneration of bone and cartilage; however, none of them address the simultaneous healing of these tissues in the complicated heterogeneous environment of the OC interface. As regulators of cell adhesion, proliferation, differentiation, angiogenesis, immunomodulation, and antibacterial activity, potential therapeutic strategies for OC defects utilizing bone and cartilage-specific peptides should be examined and investigated. Therefore, the main goal of this review is to study how they contribute to the healing of OC defects, either alone or in conjunction with other peptides and biomaterials.