Objective: To carry out a literature review on the dentin biomodification agents used in dental research. Methods: The PubMed database and collected literature were used as a resource for peer-reviewed articles to highlight the topics of dentin hierarchical structure, biomodification agents, and investigations of their laboratory and clinical applications. Results: Biomodification agents can be categorized as physical methods and chemical agents. Synthetic and naturally occurring chemical strategies present a distinctive mechanism of interaction with the tissue. Initially thought to be driven only by inter-or intra-molecular collagen-induced non-enzymatic collagen cross-linking, multiple interactions with other dentin components are fundamental for the long-term biomechanics and biostability of the tissue. Conclusion: Riboflavin is a physical agent that is difficult to obtain in industrial terms compared to natural extracts from plants such as proanthocyanidin that can be extracted from natural sources. Cardol and cardanol are industrial discard products and are a good choice for every day being produced on a large scale. Curcumin and chitosan have more accessibility in the extraction. Those of synthetic origin, such as glutaraldehyde have cytotoxic potential and carbodiimide has been a favorable substitute due to lower cytotoxic potential.