The effects of aqueous extract of Elsholtzia rugulosa Hemsl. on lipid deposition in high-fat diet-fed mice were studied. C57BL/6J mice were randomly divided into four groups (n=6 each): control (CK), high-fat diet (HFD), metformin hydrochloride (POS) intervention, and aqueous Elsholtzia rugulosa Hemsl. (HFD+Y) intervention. Except for the control group, which received a normal diet, all other groups were fed a high-fat diet for 16 weeks. The mice's body weight, fasting blood glucose, food intake, and water consumption were recorded weekly. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were conducted at weeks 14 and 15. At the end of the feeding period, organ indices and serum biochemical parameters were measured, and morphological changes in liver cells and adipocytes were observed. The results showed that aqueous Elsholtzia rugulosa Hemsl. extract could reduce body weight gain and fat accumulation in the body, leading to decreases in inguinal fat by 34.59% and epididymal fat by 45.21%. The aqueous extract improved glucose tolerance and insulin sensitivity while reducing serum triglyceride (15.54%), total cholesterol (24.69%), and alanine aminotransferase (40.78%) levels and hepatic triglyceride (36.14%) and total cholesterol (24.89%) contents. In conclusion, aqueous Elsholtzia rugulosa Hemsl. extract resulted in body weight gain, enhanced insulin sensitivity, and reduced lipid deposition in mice fed a high-fat diet. This study provides a theoretical basis for developing natural compounds to treat lipid metabolism disorders.