The extracellular matrix (ECM) serves as a dynamic scaffold that supports cellular functions and tissue integrity in multicellular organisms. The ECM plays crucial roles in tissue architecture, mechanical support, and signal transduction. This intricate network not only provides structural support but also regulates cell behavior, influencing processes like adhesion, migration, differentiation, and proliferation. ECM maintains tissue homeostasis through a delicate balance between synthesis, remodeling, and degradation. This balance is tightly controlled by various enzymes, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and others, ensuring proper tissue function and repair. Disruption of ECM dynamics, however, contributes to the pathogenesis of numerous diseases. In pathological conditions such as cancer, fibrosis, and cardiovascular diseases, ECM alterations play pivotal roles. Dysregulated ECM remodeling can promote tumor progression by facilitating invasion and metastasis, altering cell–matrix interactions, and promoting angiogenesis. In fibrotic diseases, excessive ECM deposition leads to tissue stiffening and organ dysfunction. Cardiovascular diseases involve ECM remodeling in arterial walls, affecting vessel integrity and elasticity. Understanding the ECM's role in disease pathogenesis opens avenues for therapeutic interventions. Strategies targeting ECM components or enzymes involved in ECM remodeling hold promise for treating cancer metastasis, fibrosis, and cardiovascular diseases. This chapter explores current research on ECM biology in health and disease contexts, highlighting its dual role as a structural scaffold and signaling platform.