Hydrogels are promising candidates for wound healing bandages because they can mimic the native skin microenvironment. Additionally, there is increasing growth in the use of naturally derived materials and plant-based biomaterials to produce healthcare products with healing purposes because of their biocompatibility and biodegradation properties. In this study, cellulose extracted from biodiverse sources in Ecuador was used as the raw material for the fabrication of hydrogels with enhanced antifouling properties. Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) were used to characterize the cellulose and hydrogels. In vitro and ex vivo tests were performed to evaluate the antimicrobial activity of hydrogels against Gram-negative bacteria as a model. Finally, the hydrogel synthesized with cellulose extracted from pitahaya showed improved antibacterial activity when applied over pigskin as a proof of concept for wound dressing. Therefore, the present results suggest that cellulose-based hydrogels are good candidates for application as wound dressings.