Background and Objectives: Chronic rhinosinusitis (CRS) is a complex inflammatory condition of the nasal passages that severely impairs quality of life. Type 2 CRS is characterized by eosinophilic inflammation, driven by cytokines like IL-4, IL-5, and IL-13. These cytokines are key to CRS pathogenesis and contribute to a heavy disease burden, especially with comorbidities. This study assessed dupilumab, a monoclonal antibody targeting IL-4 and IL-13 signaling, to evaluate its efficacy in reducing the disease burden in patients with CRS with nasal polyps (CRSwNP). Materials and Methods: The patients received subcutaneous dupilumab for 42 weeks. The outcomes included Nasal Polyp Score (NPS); Sino-Nasal Outcome Test (SNOT-22), Numeric Rating Scale (NRS), and Visual Analog Scale (VAS) scores; total IgE; and olfactory function. Results: Significant improvements were observed across the NPS and SNOT-22, NRS, and VAS scores after 42 weeks. Their total IgE levels were reduced, though a transient increase in peripheral eosinophilia appeared at 16 weeks. The patients also reported substantial improvements in olfactory function and high satisfaction with the treatment, supporting dupilumab’s potential in reducing both symptom severity and inflammation in CRSwNP. Conclusions: These results indicate that dupilumab may be an effective treatment for CRSwNP, offering significant symptom relief, improved olfactory function, and enhanced quality of life. High satisfaction levels suggest that dupilumab may provide therapeutic advantages over the conventional CRS treatments, though further studies are warranted to confirm its long-term benefits.