Gynostemma pentaphyllum (GP) is widely used for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China, and atorvastatin is a popular anti-hyperlipidemia drug. Based on GC/MS and metabonomic methods, this study focuses on the comparative metabolic profiling analysis of fatty acids in the plasma and liver of hyperlipidemic rats before and after treatment, in order to identify the treatment mechanism of the two drugs. Results obtained show that GP and atorvastatin can effectively improve the levels of saturated fatty acids, although atorvastatin has only a relatively weak regulatory effect on unsaturated fatty acids, whereas the traditional Chinese medicine (TCM) GP can significantly improve the levels of arachidonic acid and docosahexaenoic acid (DHA).