Objective: To investigate anti-dyslipidemic effects of hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile on HepG2 cell line. Methods: HepG2 cells were treated with hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat. IC20 was calculated using the MTT method. The cells were then pre-treated with IC20 concentrations for 24 and 48 h. Real time PCR was employed to measure expression of liver X receptor alpha (LXR α ), sterol regulatory element-binding protein-1C (SREBP-1C), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), fibroblast growth factor 21 (FGF21), peroxisome proliferator-activated receptor gamma (PPAR γ ), and low-density lipoprotein receptor (LDLR). Results: The results showed that LXR α (P=0.003, P<0.001), SREBP-1C (P<0.001, P<0.001), ACC (P=0.002, P=0.006), and FAS (P<0.001, P<0.001) were downregulated significantly, while FGF21 (P<0.001, P<0.001), PPAR 7 (P=0.004, P<0.001), and LDLR (P<0.001, P<0.001) were upregulated significantly in HepG2 cells treated with the IC20 of hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat in 24 and 48 h, respectively. Conclusions: Hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile significantly modulate the expression of some important lipid metabolism related genes, which is similar to orlistat. Trigonella foenum-graecum seed extract or its derivatives should be further investigated for their dyslipidemia effects and its complications.