Pomegranate peel is considered as an antioxidant and a nutritive by-product. It is easily available after the production of pomegranate juice. The purposes of the current research were to use the powder of pomegranate peel (PPP) as an antioxidant and a fibre-rich source to make a nutritious cupcake based on 5%, 10%, 15% and 20% PPP and investigate its effect on the weight loss of rats fed by a high-fat diet (HFD). In total, 42 female albino adult rats were included and divided into 7 groups (each group contained 6 rats). A basal diet was fed to Group 1 (G1) (negative control), a HFD was given to (G2), a HFD+ control cupcake was given to (G3), (G4) received a HFD + 5% PPP-fortified cupcake, (G5) was fed a HFD + 10% PPP-fortified cupcake, (G6) was fed a HFD + 15% PPP-fortified cupcake and (G7) was fed a HFD + 20% PPP-fortified cupcake. Food consumption, food efficiency, and body weight gain (g), the serum lipid profile and liver function were monitored. The results revealed a significant decline (p>0.05) in the weight gain of rats in G7 followed by G6, G5 and G4 and compared to G2 and G3. VLDL-C, LDL-C, total cholesterol, triglycerides, and liver enzymes (AST, ALT) were decreased by increasing the amount of PPP in the cupcake; whereas, HDL-C was increased significantly. In conclusion, pomegranate peel powder-fortified cupcakes can help with weight loss and avoid the risk of obesity, which could be incorporated into a range of foods.