The paper presents an in vitro study on the evaluation of the biocompatibility of collagen sponges extracted from the human umbilical-placental complex, with a view to their use in medical applications. Collagen, being a major structural protein of the human body, which is found especially in bone tissue in a proportion of approximately 30%, has a high applicability in bone regeneration. Bone grafting based on collagen from autologous sources is limited, and xenogeneic sources pose a risk of transmitting zoonoses, thus the use of collagen from the umbilical-placental complex would be of interest for safe use in regeneration. In this study, collagen was obtained by a modified enzymatic method, and some samples were purified using surfactants such as SDS 0.1%, SDC 1% and EDTA 1%. Samples were transformed into collagen sponges, sterilized and subjected to biocompatibility tests: MTT test (for cell viability) at 24, 48 and 72 h and cell adhesion test at 7 and 14 days, using bone cell cultures. Results indicated good cell viability (over 80%) and high cell adhesion, with an increased cell density over time and the comparison between purified and non-purified samples, suggesting that the use of surfactants does not negatively affect the biocompatibility of collagen. Overall conclusion is that collagen sponges extracted from human placenta and umbilical cord can be considered safe and effective biomaterials for medical applications, especially in oral and maxillofacial tissue reconstruction.