This study evaluates the potential effects of pumpkin seeds protein on blood pressure (BP), plasma adiponectin, leptin levels, and oxidative stress in rats with fructose-induced metabolic syndrome. Twenty four male Wistar albino rats were divided into four groups and fed a 20% casein diet, 20% casein diet supplemented with pumpkin protein, 20% casein diet with 64% D-fructose, or 20% casein diet with pumpkin protein and 64% D-fructose for 8 weeks. Contin-uous fructose feeding induced an increase in plasma insulin/glucose ratio, BP, insulin and glucose, aspartate aminotrans-ferase, alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, urea, and uric acid levels, and a decrease in the liver and muscle glycogen stores. In addition, elevated levels of total cholesterol (TC), triglycerides (TG), and leptin and lowered adiponectin levels were observed in rats fed a fructose-enriched diet. These groups also exhibited lower plasma levels of ascorbic acid and glutathione, higher thiobarbituric acid-reactive substances, hydroperoxide, carbonyl, and nitric oxide in both the liver and kidneys than rats fed the control diet. Interestingly, pumpkin seed protein treatment significantly counteracted alterations induced by fructose improving glucose, insulin, BP, TG, TC, ALT, and ALP levels, increasing liver and muscle glycogen stores, adiponectin level, and adiponectin/leptin ratio, and reducing plasma leptin lev-els. In addition, rats fed pumpkin protein with a high-fructose diet improved oxidative stress in the liver and kidneys. In conclusion, proteins from Cucurbita pepo L. seeds effectively improve metabolic parameters and protect against oxidative stress induced by a high-fructose diet.