The present study consists of analyzing the phytochemical composition of Ipomoea batatas leaf powders and evaluating their antihyperlipidemic effect on rats receiving a high-fat diet. Ipomoea batatas leaves were collected from four agroecological areas of Cameroon, and powders were obtained after washing, drying, grinding, and sieving. Standard analytical methods were used to determine the phytochemical composition of two varieties (IRAD-tib1yellow-V1 and IRAD-1112white-V2) from North Z1, Adamawa Z2, West Z3, Center Z4. The effect of I. batatas leaf powder on lipid metabolism was assessed in vivo by feeding different groups of rats with a high-fat diet supplemented with 5 and 10% of I. batatas leaf powder during 30 days. At the end of the experimentation, total cholesterols, triglycerides, LDL- (low-density lipoprotein-) cholesterol, HDL- (High-density lipoprotein-) cholesterol, ASAT (aspartate aminotransferase), ALAT (alanine aminotransferase), and creatinine were measured using commercial enzymatic kits (Spinreact, Spain). The results of phytochemical analysis of I. batatas leaf powders revealed that the total phenol content ranged from 660.173 mg GAE/100 gDW (Z1V2) to 657.76 mg GAE/100 gDW (Z3V2), the flavonoids content ranged from 282.25 mgEC/100 gDW (Z3V1) to 325.05 mgEC/100 gDW (Z4V2), and the anthraquinone content ranged from 324.05 mg/100 gDW (Z3V2) to 326.72 mg/100 gDW (Z4V2). The total antioxidant capacity ranged from 19.00 (Z1V1) to 23.48 mg AAE/gDW (Z3V2), while the IC50 ranged from 1.58 mg/mL (Z1V1) to 3.08 mg/mL (Z3V2). Rats fed a high-fat diet and supplemented with 5 and 10% of I. batatas leaf powder showed a significant (
p
<
0.05
) reduction in body weight compared to the control with a reduction rate ranging from 6 to 10%. The consumption of I. batatas leaf powder for 30 days significantly (
p
<
0.05
) reduced serum total cholesterol, LDL-cholesterol, triglycerides, ALAT, and creatinine level. These results suggest the use of I. batatas leaves as a phytomedicine in the treatment of cardiovascular diseases.