The in vitro micellar cholesterol displacement assay has been used to identify peptides that may potentially reduce cholesterol in vivo. Two of these peptides, LPYPR and WGAPSL, derived from soybean protein (SP) that have been reported to displace cholesterol from micelles were tested by feeding them as a part of a hypercholesterolemic diet to mice for 3 weeks. Except reduction of very low-density lipoprotein cholesterol (VLDL-C) and triglyceride contents, the peptide-containing diets increased plasma cholesterol content with the increasing dose of the peptides. Mice fed diets supplemented with the peptides also had lower fecal bile acid excretion. Negative correlations between fecal bile acid excretion and plasma total cholesterol content (r = -0.876, P = 0.062) and non-HDL-C content (r = -0.831, P = 0.084) were observed. The mRNA levels of the genes for cholesterol and bile acid metabolism, CYP51, LDLR, CYP7A1, and LPL, were up-regulated in mice fed diets supplemented with peptides except the group fed the low dose of WGAPSL. The results suggested that higher plasma total cholesterol content possibly due to lower fecal steroid excretion as well as lower VLDL-C and triglyceride contents might due to the up-regulated expression levels of the genes CYP51, LDLR, and LPL.