Abstract Lactobacillus plantarum, which exerts a variety of probiotic functions, has been recognized as a supplement for human foods with a widespread application. In this work, the cholesterol-lowering mechanisms of marine L. plantarum Lp10 were investigated by combining the analyses of transcriptome and quantitative real-time PCR. Results indicated that bile salt hydrolase (BSH) activity and extracellular polysaccharides (EPSs) adsorption were both responsible for cholesterol reduction. In this process, 11.1 million clean reads and 384 differentially expressed genes, including 79 up-regulated genes and 225 down-regulated genes, were obtained by transcriptome analysis. It was considered that EPS adsorption was mainly responsible for the cholesterol reduction without the influence of bile salt. Further analysis showed that the co-precipitation of cholesterol and deconjugated bile acids induced by BSH1 and BSH2 may play important role in the tolerance and reduction of cholesterol of strain under the stress condition with bile salt, in which, interestingly, the expressions of bsh3 and bsh4 were suppressed. In conclusion, the cholesterol-lowering mechanisms of marine L. plantarum Lp10 was investigated and it was considered as a potential strain for the application in cholesterol reduction.