Background: Hyperlipidemia is one of important risk factors involved in the development of cardiovascular diseases. One therapy involves theinhibition of cholesterol production by 3-hydroxy-3-methylglutarylcoenzyme A(HMG-CoA)reductase inhibitors. The drugs used in the management of the disease have showed some side effects. Therefore, it is crucialto evaluate the potential of plants for the discoveryof novel bioactive compounds. With such aims, the effects of some plants methanolic extracts on HMG-CoAreductase activity were tested. Materials and Methods: Methanolic extracts of fifteen plant species were investigated. All extracts were screened for their HMG-CoA reductase inhibitory activity, at 0.1 mg/mL final concentration in reaction mixture. Assay method was based on spectrophotometric study of changes in NADPH absorption in 340 nm, in the presence of enzyme and mevalonate, with microplate method. Paravastatine was used as a positive control. Results: Methanolic extracts of Aethionemamembranaceum, Chaerophyllummacropodum, Hypericumasperulum, Hypericumscabrum, Muscarilongipes, and, Trifoliumpretens presented strong inhibition of HMG-CoA reductase (more than 50%) at 1 mg/mL, withChaerophyllummacropodum, Trifoliumpretens and Hypericumasperulum being the most potent, showing complete inhibition of the enzyme. Their IC50 values were 0.091 and 0.097, and 0.095 mg/mL, respectively. Our results indicate that these plants would be interesting to purify active constituents as potential drugs for hyperlipidemia.