Injectable hydrogel is a very promising biomaterial application in the biomedical field, especially for minimally invasive therapeutic applications due to its ability to be injected in liquid or semi-liquid form and undergo in situ gelation at the target site. Hydrogel technology based on natural multi-biopolymers such as carboxymethyl cellulose (CMC), sodium alginate (SA), and chitosan (CS) is increasingly attracting attention due to its biocompatibility, biodegradability, and biological activity that support the healing process. The use of calcium chloride (CaCl2) as an ionic crosslinker allows the formation of a stable and strong gel through ionic interactions with carboxylate groups in alginate, allowing the hydrogel to have optimal mechanical and physical properties for clinical applications. In this study, a stepwise factorial experimental design was used to develop an injectable hydrogel formulation based on a combination of CMC, SA, and CS with CaCl as a crosslinker. The swelling, degradation, injectability, rheological properties, and surface morphology were characterized using scanning electron microscopy (SEM). The composition of CMC-SA-CS with a concentration of 3%:2%:2% produced the best results with a gelation time of 7.80±0.18 seconds, controlled degradation 34.01±2.33%, low swelling% of 14.90±0.08%, injectability of 87.09±0.72%, and stability expressed by a high elastic modulus (G’) of 46,2 kPa. This study contributes significantly to the development of injectable biomaterials that are applicable and efficient for minimally invasive therapy, thereby opening up opportunities for the development of safer and more effective therapies. © 2026 Faculty of Engineering, Universitas Indonesia. All rights reserved.