Metabolic dysfunction-associated steatotic liver disease (MASLD), driven by modern sedentary lifestyles and high-fat diets, represents a global health crisis. Available therapeutic options suffer from drawbacks such as a short plasma half-life and the requirement for frequent dosing. To address these limitations, we designed a recombinant fusion protein, pET28a-SUMO-Temporin-DARPin. Temporin, a peptide isolated from the skin secretions of the European brown frog (Rana temporaria), has metabolic regulatory and anti-inflammatory potentials; however, its translation is hindered by rapid renal clearance and a short circulation time. DARPin, an anti-human serum albumin (anti-HSA DARPin) known for its structural robustness and target binding, acts as a long-acting platform to extend half-life dramatically. In vivo evaluation in an obese mouse model revealed that a single administration of the Temporin-DARPin protein at 200 nmol/kg demonstrated maintenance of glycemic control, keeping below 170 mg/dl for the first few days. Furthermore, administration of Temporin-DARPin twice a week for 6 weeks resulted in a reduction in body weight, daily food intake, and a significant lowering of blood glucose compared to the native Temporin peptide and control groups. Most notably, an improvement was observed in the fatty liver condition. Overall, our findings suggest that the SUMO-Temporin-DARPin platform represents a highly promising therapeutic candidate for the management of MASLD.