Acellular dermal matrix (ADM) is derived from natural skin by removing the entire epidermis and the cell components of dermis, but retaining the collagen components of dermis. It can be used as a therapeutic alternative to “gold standard” tissue grafts and has been widely used in many surgical fields, since it possesses affluent predominant physicochemical and biological characteristics that have attracted the attention of researchers. Herein, the basic science of biologics with a focus on ADMs is comprehensively described, the modification principles and technologies of ADM are discussed, and the characteristics of ADMs and the evidence behind their use for a variety of reconstructive and prosthetic purposes are reviewed. In addition, the advances in biomedical applications of ADMs and the common indications for use in reconstructing and repairing wounds, maintaining homeostasis in the filling of a tissue defect, guiding tissue regeneration, and delivering cells via grafts in surgical applications are thoroughly analyzed. This review expectedly promotes and inspires the emergence of natural raw collagen-based materials as an advanced substitute biomaterial to autologous tissue transplantation.