In biomaterials research, using one or two components to prepare materials is common. However, there is a growing interest in developing materials composed of three components, as these can offer enhanced physicochemical properties compared to those consisting of one or two components. The introduction of a third component can significantly improve the mechanical strength, biocompatibility, and functionality of the resulting materials. Cross-linking is often employed to further enhance these properties, with chemical cross-linking agents being the most widely used method. This article provides an overview of the chemical agents utilized in the cross-linking of three-component biomaterials. The literature review focused on cases where the material was composed of three components and a chemical substance was employed as the cross-linking agent. The most commonly used cross-linking agents identified in the literature include glyoxal, glutaraldehyde, dialdehyde starch, dialdehyde chitosan, and the EDC/NHS mixture. Additionally, the review briefly discusses materials cross-linked with the MES/EDC mixture, caffeic acid, tannic acid, and genipin. Through a critical analysis of current research, this work aims to guide the development of more effective and safer biopolymeric materials tailored for biomedical applications, highlighting potential areas for further investigation and optimization.