This review discusses the role of matrix metalloproteinases (MMPs) as biomarkers and therapeutic targets in colitis-associated cancer (CAC). CAC is a type of colorectal cancer (CRC) that develops in the context of chronic inflammatory bowel disease (IBD), primarily ulcerative colitis and Crohn's disease. MMPs are a family of zinc- and calcium-dependent endopeptidases that play key roles in extracellular matrix (ECM) degradation, which is essential for tumor expansion, invasion, and metastasis. While the role of MMPs in sporadic CRC is well understood, their role in CAC is less clear. This review aims to summarize the current understanding of MMPs in CAC, their potential as biomarkers, and their role in therapeutic approaches. MMPs are classified into several subgroups, including collagenases, gelatinases, stromelysins, matrilysins, metalloelastase, enamelysin, epilysin, and membrane-type MMPs. Each subgroup has distinct domain organization and substrate specificity. MMPs are regulated at multiple levels, including transcriptional, post-transcriptional, and proteomic levels. They are involved in various biological processes, including cell migration, adhesion, and inflammation. Dysregulated MMP expression or function can broadly impact health and disease, and are associated with conditions such as fibrotic diseases, vasculopathies, and cancer progression. In CAC, chronic inflammation plays a key role in the development and progression of the disease. MMPs are involved in the pathogenesis of CAC, and their expression and activity are altered in CAC compared to non-colitis-associated CRC. Some MMPs, such as MMP-9, may act as tumor suppressors in CAC, while others, like MMP-7, may contribute to the development of CAC. The roles of MMPs in CAC are complex and context-dependent, and their potential as biomarkers and therapeutic targets is an area of active research. Several MMP inhibitors have been developed and tested in clinical trials for the treatment of CRC and CAC. These include synthetic MMP inhibitors, such as Marimastat and Prinomostat, as well as monoclonal antibodies, such as Andecaliximab. However, the clinical application of MMP inhibitors has been limited by challenges such as low bioavailability, toxicity, and the need for more targeted delivery. Despite these challenges, MMP inhibitors remain a promising area of research for the treatment of CAC and other cancers. The review highlights the need for further research into the role of MMPs in CAC and the development of more effective therapeutic strategies.This review discusses the role of matrix metalloproteinases (MMPs) as biomarkers and therapeutic targets in colitis-associated cancer (CAC). CAC is a type of colorectal cancer (CRC) that develops in the context of chronic inflammatory bowel disease (IBD), primarily ulcerative colitis and Crohn's disease. MMPs are a family of zinc- and calcium-dependent endopeptidases that play key roles in extracellular matrix (ECM) degradation, which is essential for tumor expansion, invasion, and metastasis. While the role of MMPs in sporadic CRC is well understood, their role in CAC is less clear. This review aims to summarize the current understanding of MMPs in CAC, their potential as biomarkers, and their role in therapeutic approaches. MMPs are classified into several subgroups, including collagenases, gelatinases, stromelysins, matrilysins, metalloelastase, enamelysin, epilysin, and membrane-type MMPs. Each subgroup has distinct domain organization and substrate specificity. MMPs are regulated at multiple levels, including transcriptional, post-transcriptional, and proteomic levels. They are involved in various biological processes, including cell migration, adhesion, and inflammation. Dysregulated MMP expression or function can broadly impact health and disease, and are associated with conditions such as fibrotic diseases, vasculopathies, and cancer progression. In CAC, chronic inflammation plays a key role in the development and progression of the disease. MMPs are involved in the pathogenesis of CAC, and their expression and activity are altered in CAC compared to non-colitis-associated CRC. Some MMPs, such as MMP-9, may act as tumor suppressors in CAC, while others, like MMP-7, may contribute to the development of CAC. The roles of MMPs in CAC are complex and context-dependent, and their potential as biomarkers and therapeutic targets is an area of active research. Several MMP inhibitors have been developed and tested in clinical trials for the treatment of CRC and CAC. These include synthetic MMP inhibitors, such as Marimastat and Prinomostat, as well as monoclonal antibodies, such as Andecaliximab. However, the clinical application of MMP inhibitors has been limited by challenges such as low bioavailability, toxicity, and the need for more targeted delivery. Despite these challenges, MMP inhibitors remain a promising area of research for the treatment of CAC and other cancers. The review highlights the need for further research into the role of MMPs in CAC and the development of more effective therapeutic strategies.