The aim of this study was to investigate the effect of Lactobacillus plantarum and Bacillus coagulans on serum lipid profile and lowering potential of probiotic in hypercholesterolemic rats. Twenty-eight male Wistar rats were divided into four groups as follows: (1) control group, fed standard commercial diet; (2) HC group, fed high-cholesterol diet; (3) HC + LP group, fed high-cholesterol diet and gavaging of L. plantarum; and (4) HC + BC group fed high-cholesterol diet and gavaging of B. coagulans. After 28 and 50 days, serum lipid profile; serum ALT and AST; the body and organ weights; fecal total count; Enterobacteriaceae, L. plantarum, and B. coagulans counts; and blood glucose tolerance were measured. We observed that levels of triglyceride, cholesterol, LDL, VLDL, and atherogenic index in serum were significantly lower in the HC + probiotic groups. Also, serum ALT and AST were significantly decreased in probiotic-treated groups. In addition, we found that feeding of a high-cholesterol diet for 50 days produced significant increases in the body weight, in addition to the fact that the administration of L. plantarum and B. coagulans has considerably reduced the body weight gain. B. coagulans and L. plantarum can survive passing through the upper-gastrointestinal tract after oral feeding to the rats and colonized in their colon. These bacteria could be exploited as a potential biotherapeutic remedy to reduce TC, TG, LDL, VLDL, and atherogenic index in hypercholesterolemic condition.