BACKGROUND: Channa striata has several good nutrients, including 70% protein, 20% albumin, complete amino acids, zinc, selenium, and iron. However, no study has investigated the chitosan-PEG nanoparticles based on Channa striata protein hydrolyzate. This study’s purpose was to determine the role of 10% Channa striata protein hydrolyzate, chitosan-PEG 4000 nanoparticles, and chitosan-PEG 6000 nanoparticles in reducing diabetes mellitus in diabetic rats.METHOD: A randomized pretest-posttest control group design was used, with male Sprague–Dawley rats being divided into five groups: STZ, acarbose, hydrolyzate, chitosan-PEG 4000 nanoparticles, and chitosan-PEG 6000 nanoparticles. Diabetes was induced by a single injection of streptozotocin at 1 ml in each formulation. Blood glucose levels were analyzed using a glucometer 7, 14, and 21 days after treatment. The CHOD-PAP method was used to analyze the lipid profile. Pancreas and liver histology analyses were carried out using a microscope.RESULTS: The formulation of 10% Channa striata protein hydrolyzate and PEG 6000 was the most effective in lowering blood glucose concentrations, and the response was close to the acarbose result. The glucose concentration decreased after daily oral administration of chitosan-PEG nanoparticles for 21 days. The plasma cholesterol, triglycerides, LDL, and HDL concentrations were lower in treated than in untreated diabetic rats.CONCLUSION: This study concluded that the formulation of 10% Channa striata protein hydrolyzate and chitosan-PEG 6000 nanoparticles was more effective than acarbose.KEYWORDS: Diabetes mellitus, Chitosan nanoparticles, Channa striata, blood glucose, lipid profile