Abstract: Matrix metalloproteinases (MMPs) acquired their names because they depend on metal ions such as Ca²⁺ and Zn²⁺ as their cofactors. Members of this family of proteins share a similar structure consisting of five functionally distinct structural domains. MMPs, including MMP-1, MMP-3, MMP-9, and MMP-13, are key substances that promote cartilage matrix degradation and play an important role in the occurrence and progression of osteoarthritis (OA). MMPs boost the development of OA through the degradation of extracellular matrix proteins of chondrocytes, the promotion of inflammation, and other mechanisms, and are hence attracting extensive and increasing attention from the medical community. OA is a common degenerative disease that occurs in the joints and is associated with aging, metabolism, infections, genetics, exercise, and other predisposing factors. The pathological changes it causes can lead to a series of clinical symptoms such as joint pain, morning stiffness, and restricted joint movement, severely affecting patients' quality of life. The pathogenic mechanism of this highly prevalent disease is still unclear. At present, there is no effective treatment available for disease improvement. In the future, selective inhibition of MMPs, the key enzymes, may become an effective therapeutic approach. Focusing on the pathogenic effects of MMPs in OA, we herein reviewed the latest findings on the role of MMPs in the occurrence and progression of OA.