To ensure the health and safety of patients, all dental biomaterials must undergo screening assays to determine their biocompatibility. The objective of this review is to explain the framework of a test program as well as the worldwide biocompatibility requirements. The test program mandates that materials be structurally evaluated into four parts: general evaluations in pre clinical and clinical settings for toxicity and local tissue irritation. There are different screening assay types available, and it is crucial to comprehend the benefits and restrictions of each form of assay so that they can be properly chosen and correctly understood. In terms of the chemical composition of dental materials, tissue engineering, stem cells, genetic transfer, biomaterials, and growth factor therapies, new scientific developments are now being developed. These novel treatments increase the chances of restoring and regenerating oral tissues, but they can also expose patients to new risks. These new technologies must be demonstrated to be safe and not harmful to human health before being used in clinical settings. To assess these novel treatments, a systematic biocompatibility assessment and recommendations on assay selection are provided.