Background:  Obesity has become a prevalent issue worldwide, leading to various complications such as hyperlipidemia, diabetes, and cardiovascular problems. Statins, as FDA approved anti-hyperlipidemic drugs still pose some concerns upon their administration. Recently, researchers have looked for natural products as an alternative to manage hyperlipidemia and obesity. Aim: This work aimed to study the hypolipidemic effect of Lepidium sativum garden cress (GC) from differen preparations; orally administered seeds, and hydrogel, in comparison to atorvastatin. Methods:  GC hydrogel was prepared from the GC aqueous extract and pharmaceutically evaluated for it pH, spreadability, seeds content, homogeneity, rheology, and in vitro release. The rat’s body weight, bloo glucose levels, total lipid profile, and liver biomarkers were evaluated on obese rats for one month. In addition, the histopathology study was also performed. Results: GC hydrogel had acceptable pharmaceutical properties and showed a sustained release performance over 24h. Oral and topical GC significantly reduced the lipid profiles, blood sugar and AT, AST level than the negative control group and comparable to atorvastatin. It was found that oral GC showed significant effect on the percentage decrease in the rat’s body weight than the applied hydrogel. Histopathology study revealed a better outcome in the histological structure of pancreas and liver compared with rats feed on high fat diet post-treatment for one month. Conclusion:  GC orally administered, or topically applied hydrogel could be a promising, safe alternative formulation to atorvastatin in managing hyperlipidemia and normalizing body weight of obese rats