Sea buckthorn has lipid-lowering properties and is widely used in the development of functional foods. In this study, a probiotic (Lactobacillus plantarum, Lp10211) with cholesterol-lowering potential and acid and bile salt resistant was screened for the fermentation of sea buckthorn juice. Changes in the active ingredients, such as sugars and phenolics, before and after fermentation, as well as their in vitro lipid-lowering activities, were compared. The contents of reducing and total sugars decreased substantially after fermentation. Lp10211 primarily utilized fructose for growth and reproduction, with a utilization rate of 76.9%. The phenolic compound content of sea buckthorn juice increased by 37.06% after fermentation and protected the phenolic components from degradation (protocatechuic and p-coumaric acids) and produced new polyphenol (shikimic acid). Enhanced inhibition of pancreatic lipase activity (95.42%) and cholesterol micellar solubility (59.15%) was evident. The antioxidant properties of the fermentation broth were improved. Notably, Lp10211 preserved the color and reversed browning in sea buckthorn juice. The collective findings indicate that fermentation of sea buckthorn juice by Lp10211 may enhance the functional components and lipid-lowering activity of sea buckthorn, which may provide a new approach for the development of lipid-lowering foods.