Adipogenesis is linked to obesity through the proliferation and deposit of preadipocytes as adipose tissues occur at various sites in the body. This study was investigated the effects of Euclea racemosa subsp. schimperi extracts on lipase enzymes in order to identify the most active fractions. Then, the bioactive fraction was injected on the high-fat diet adipose tissue (HFD-AD). Afterward, the lipid profile, oxidant/antioxidant parameter, and lipid accumulation were measured inside the cells. Finally, LCMS/MS for this fraction was performed. The aqueous fraction exhibited a stronger inhibitory effect on lipase enzymes with an IC50 of 18.15±1.24 µg/ml compared to orlistat's (IC50 of 5.27±0.62 µg/ml). The aqueous fraction and methylsulfonylmethane (MSM) were administered to HFD-AD cells at concentrations of (0.529±0.025 and 0.093±0.02 µg/ml), respectively. There was no significant difference (p > 0.05) between the effects of MSM and the aqueous fraction on controlling lipids profile parameters (triglycerides (TG), cholesterol (C), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C)). Furthermore, the aqueous Fr. reduced lipid accumulation, malondialdehyde (MAD), and nitric acid (NO) activity compared to untreated cells with a non-significant difference compared to the MSM (p > 0.05). Additionally, the aqueous Fr. showed an increase in total antioxidant capacity (TAC) and catalase (CAT) activity significantly compared to the MSM (p < 0.05). In conclusion, The aqueous Fr. improved lipid accumulation, lipid profile, oxidative stress, and antioxidant effects. These activities attributed to various compounds identified by LC MS/MS.