Probiotics are prospective for the prevention and treatment of cardiovascular diseases. Until now, systematic studies on the amelioration of hypercholesterolemia have been rare in terms of (cholesterol metabolism and transportation, reshaping of gut microbiota, as well as yielding SCFAs) intervention with lactic acid bacteria (LAB). In this study, strains ofLactiplantibacillus plantarum, WLPL21, WLPL72, and ZDY04, from fermented food and two combinations (Enterococcus faeciumWEFA23 withL. plantarumWLPL21 and WLPL72) were compared for their effect on hypercholesterolemia. Comprehensively, with regard to the above aspects,L. plantarumWLPL21 showed the best mitigatory effect among all groups, which was revealed by decreasing total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, upregulated cholesterol metabolism (Cyp27a1,Cyp7b1,Cyp7a1, andCyp8b1) levels in the liver, cholesterol transportation (Abca1,Abcg5, andAbcg8) in the ileum or liver, and downregulatedNpc1l1. Moreover, it reshaped the constitution of gut microbiota; specifically, the ratio ofFirmicutestoBacteroidetes(F/B) was downregulated; the relative abundance ofAllobaculum,Blautia, andLactobacilluswas upregulated by 7.48–14.82-fold; and that ofLachnoclostridiumandDesulfovibriowas then downregulated by 69.95% and 60.66%, respectively. In conclusion,L. plantarumWLPL21 improved cholesterol metabolism and transportation, as well as the abundance of gut microbiota, for alleviating high-cholesterol-diet-induced hypercholesterolemia.