Aim. Recent studies suggested that weight reduction under energy restriction required protein supplementation. Moreover, a significant decrease in serum cholesterol and triglycerides was observed when milk-serum proteins and, in particular, their hydrolyzed peptides were compared to milk casein. Methods. Six Sprague-Dowley rats were fed with the standard diet for 8 weeks. Eighteen rats were fed with the obesity-producing diet for 4 weeks. After this period and for the remaining 4 weeks, these rats were divided into 3 groups, the 1(st) was fed with the obesity-diet, the 2(nd) and the 3(rd) were fed with the casein-and with the hydrolyzed milk-serum peptides-restricted diet, respectively. Results. Treatment with the obesity-diet, compared to standard-diet, induced an increase in the body weight and fat content, with a decrease in protein mass and dehydration state. There was also an increase in blood levels of cholesterol, triglycerides and glucose. The lipoperoxides content in the plasma, heart, brain and liver had also increased, while the content of glutathione and ATP and the membrane fluidity in the liver had significantly decreased. The administration of the restricted caloric diet, in particular the one containing the hydrolyzed peptides were capable of an improvement of all these parameters. Conclusion. The metabolic modifications induced by the hydrolyzed peptides-restricted diet contribute to control better the over-weight thus reducing the risk of the onset of the dismetabolic pathologies correlated to it.