Obesity is a global disease that threatens millions of people causes death every year as result of overweight complications. Furthermore, obesity is a main cause of cardiovascular disease and type 2 diabetes. Preventing and treating obesity has been a prevailing concern for many countries also the uptake of natural remedies become a primary focus of researchers to get safer and more efficient drugs. In this article we evaluate the effect of green seaweed; Enteromorpha intestinalis as a therapeutic supplement for obesity and obesity-related diseases. Female albino rats were divided into four groups; control negative (CN), control positive (CP) and positive treated with E. intestinalis crude extract (M) and spirulina powder supplement (SP). Female rats were fed by algal extract for 4 weeks and weight gain change was determined, at the end of the treatment period blood was collected and different biochemical parameters were measured to evaluate the anti-hyperlipidemic, anti-inflammatory, and antiobesity effects of the E. intestinalis crude extract compared to spirulina microalgae powder supplement on rats fed a high-fat diet. E. intestinalis extract (M) showed a significant effect in suppressing weight gain. Also, the M group showed a significant effect in suppressing plasma total cholesterol and triglycerides recording about 118 mmolL-1 and 62 mmolL-1, respectively which is nearly the same as the control negative group. Also, low-density lipoprotein, leptin, glucagon-like peptide-1 and peptide y y recorded about 60.55 mmolL-1, 8.63 mmolL-1 11.93 mmolL-1, and 102.8 mmolL-1so usage of E. intestinalis crude extract has positively effect in treatment and prevention of obesity as well as Spirulina supplement.