Osteoarthritis (OA) is a chronic joint disease characterized by irreversible cartilage degradation. MMP (matrix metalloproteinase) inhibitors represent a new approach to slowing OA progression by addressing cartilage degradation mechanisms. However, the success of preclinical studies failed to be translated into clinical application. One of the possible reasons is that the disease models in preclinical study can't reflect the biological complexity of human disease. Hydrogel-based cartilage constructs as in vitro models have shown promise as preclinical testing platforms due to their enhanced physiological relevance, improved prediction to human response, high-throughput drug screening, and ease of use. Metalloproteinase-13 (MMP-13) is thought to be a major contributor to the degradation of articular cartilage in OA by aggressively breaking down type II collagen. This study focused on testing MMP-13 inhibitors using a GelMA-alginate hydrogel-based OA model induced by cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). The results demonstrated a significant inhibition of type II collagen breakdown by measuring C2C concentration using ELISA after treatment with MMP-13 inhibitors. Therefore, the study highlights the GelMA-alginate hydrogel-based OA model as an alternative to human-sourced cartilage explants for in vitro drug screening, which can improve the predictability and relevance of preclinical evaluations of MMP-13 inhibitors for osteoarthritis, thereby complementing existing 2D culture, cartilage explant, and animal model studies and addressing the translational gap observed in clinical trials.