This review discusses the development and biomedical applications of hydrogels based on proteins cross-linked with carbonyl derivatives of oxidized polysaccharides. The hydrogels are formed by introducing carbonyl groups into polysaccharide chains through oxidation, which enhances their reactivity and cross-linking potential. These hydrogels exhibit tunable mechanical properties, improved biocompatibility, and dynamic behavior, making them suitable for various biomedical applications, including tissue engineering, drug delivery, and wound healing. Polysaccharides, such as alginate, chitosan, pullulan, carboxymethylcellulose, and pectin, are modified through oxidation to introduce carbonyl groups. These modifications enhance the polysaccharides' functionality, enabling them to form stable cross-linked networks with proteins. The cross-linking is often achieved through Schiff base formation, which involves the reaction between carbonyl groups in modified polysaccharides and amino groups in proteins. The review highlights the importance of oxidation methods, such as enzymatic and periodate oxidation, in introducing carbonyl groups into polysaccharides. These methods allow for precise control over the degree of oxidation, which influences the hydrogels' properties. For example, periodate oxidation can cleave vicinal diols in polysaccharides, leading to the formation of aldehyde groups that can be cross-linked with proteins. The hydrogels derived from these modified polysaccharides and proteins have diverse applications, including injectable hydrogels for drug delivery, hydrogel films for wound dressings, and micro/nanoparticles for targeted drug release. The review also discusses the biocompatibility, biodegradability, and mechanical properties of these hydrogels, emphasizing their potential in biomedical applications. Overall, the review underscores the significance of carbonyl-modified polysaccharides in the development of advanced hydrogels with tailored properties for various biomedical uses. The combination of polysaccharides and proteins in these hydrogels offers unique advantages, such as enhanced functionality, tunable mechanical properties, and improved biocompatibility, making them promising materials for future biomedical applications.This review discusses the development and biomedical applications of hydrogels based on proteins cross-linked with carbonyl derivatives of oxidized polysaccharides. The hydrogels are formed by introducing carbonyl groups into polysaccharide chains through oxidation, which enhances their reactivity and cross-linking potential. These hydrogels exhibit tunable mechanical properties, improved biocompatibility, and dynamic behavior, making them suitable for various biomedical applications, including tissue engineering, drug delivery, and wound healing. Polysaccharides, such as alginate, chitosan, pullulan, carboxymethylcellulose, and pectin, are modified through oxidation to introduce carbonyl groups. These modifications enhance the polysaccharides' functionality, enabling them to form stable cross-linked networks with proteins. The cross-linking is often achieved through Schiff base formation, which involves the reaction between carbonyl groups in modified polysaccharides and amino groups in proteins. The review highlights the importance of oxidation methods, such as enzymatic and periodate oxidation, in introducing carbonyl groups into polysaccharides. These methods allow for precise control over the degree of oxidation, which influences the hydrogels' properties. For example, periodate oxidation can cleave vicinal diols in polysaccharides, leading to the formation of aldehyde groups that can be cross-linked with proteins. The hydrogels derived from these modified polysaccharides and proteins have diverse applications, including injectable hydrogels for drug delivery, hydrogel films for wound dressings, and micro/nanoparticles for targeted drug release. The review also discusses the biocompatibility, biodegradability, and mechanical properties of these hydrogels, emphasizing their potential in biomedical applications. Overall, the review underscores the significance of carbonyl-modified polysaccharides in the development of advanced hydrogels with tailored properties for various biomedical uses. The combination of polysaccharides and proteins in these hydrogels offers unique advantages, such as enhanced functionality, tunable mechanical properties, and improved biocompatibility, making them promising materials for future biomedical applications.