Microbial resistance is the first morbidity and mortality cause for patients as usually a secondary infection. Additionally, the MOF is a promising material that shows a nice activity in this field. However, these materials need a good formulation to enhance biocompatibility and sustainability. Cellulose and its derivatives are well as filers for this gap. In this presented work, a novel green active system based on carboxymethyl cellulose and Ti-MOF (MIL-125-NH2@CMC) modified with thiophene (Thio@MIL-125-NH2@CMC) was prepared by a post-synthetic modification (PSM) route based. FTIR, SEM and PXRD were utilized to characterize nanocomposites. In addition, transmission electron microscopy (TEM) was used to corroborate the nanocomposites' particle size and diffraction pattern as well as the DLS affirmed the size as 50 and 35 nm for MIL-125-NH2@CMC and Thio@MIL-125-NH2@CMC, respectively. The formulation of the nanocomposites was validated by physicochemical characterization techniques, while morphological analysis confirmed the nanoform of the prepared composites. The antimicrobial, antiviral and antitumor properties of MIL-125-NH2@CMC and Thio@MIL-125-NH2@CMC were assessed. Antimicrobial testing revealed that Thio@MIL-125-NH2@CMC possesses greater antimicrobial activity than MIL-125-NH2@CMC. Additionally, Thio@MIL-125-NH2@CMC demonstrated promising antifungal activity againstC. albicansandA. nigerwhere MICs were 31.25 and 0.97 µg/mL, respectively. Also, Thio@MIL-125-NH2@CMC exhibited antibacterial activity againstE. coliandS. aureuswhere MICs were 1000 and 250 µg/mL, respectively. In addition, the results demonstrated that Thio@MIL-125-NH2@CMC displayed promising antiviral activity against both HSV1 and COX B4, with antiviral activities of 68.89% and 39.60%, respectively. Furthermore, Thio@MIL-125-NH2@CMC exhibited potential anticancer activity against MCF7 and PC3 cancerous cell lines, where IC50was 93.16 and 88.45%, respectively. In conclusion, carboxymethyl cellulose/sulfur-functionalized Ti-based MOF composite was successfully synthesized which had antimicrobial, antiviral and anticancer activities.