Tissue engineering is a growing field with multidisciplinary players in biology, medicine, and bioengineering, aiming to maintain, restore, or enhance tissue and organ function. The extracellular matrix (ECM) plays a fundamental role in tissue development, providing critical biochemical and biomechanical cues that regulate cellular behavior and signaling. Although its composition varies across different tissues and developmental stages, matrix macromolecules influence cell functional processes in every tissue. Alterations in ECM composition and/or organization are implicated in a wide range of pathological conditions, including fibrosis, cancer, and neurodegenerative diseases, underscoring its significance in both disease progression and regenerative medicine. ECM-based bioscaffolds have emerged as pivotal tools for recreating the native cellular microenvironment. Based on the origin of their components, these scaffolds can be classified into three main categories: natural, synthetic, and hybrid. While exhibiting both advantages and disadvantages, hybrid scaffolds, combining natural and synthetic materials, aim to optimize the biological activity and mechanical performance of the engineered constructs. Key properties, such as mechanical strength, elasticity, porosity, biocompatibility, and biodegradability are essential to their function and integration into host tissues. Applications of ECM-based bioscaffolds span a range of engineering/regenerative strategies, including cartilage, bone, cardiac, and neural tissue engineering and skin wound healing, among others. Despite promising advances, challenges remain in standardization, scalability, and immune response modulation, with future directions being directed toward improving ECM-based biomimetic platforms for regenerative medicine applications.