Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the progressive loss of articular cartilage and the destruction of joint structures. This study investigates the potential role of sea cucumber peptides in treating OA. Through computer simulations of gastrointestinal digestion and online database predictions, bioactive peptides from sea cucumber protein were identified. Using network pharmacology, molecular docking, and quantum chemical calculations, a sea cucumber peptide candidate (FDPVIEEYHNGF) with strong anti-OA activity was virtually screened. Further analysis suggests that this peptide may alleviate OA by modulating the IL-17 and TNF signaling pathways, inhibiting inflammation, collagen degradation, and the activity of matrix metalloproteinases (MMPs). The sea cucumber peptide may form hydrogen bonds with MMP9 and IL-17RA, a potential core target for OA, thereby influencing the related signaling pathways, reducing inflammation, intervening in extracellular matrix remodeling, and mitigating collagen degradation. This study provides new insights into the application of sea cucumber peptides as functional food ingredients in the development of therapeutic foods for OA.