Propionate and butyrate are proven capable of decreasing plasma cholesterol. However, their undesired odor and unpleasant smell limit their direct application as a dietary supplement. In contrast, their respective triacylglycerols tributyrin (Tb) and tripropionin (Tp) are odorless and can be directly used as healthy supplements. In view that no study has investigated the relative biological potency of Tb and Tp, the present study was designed to compare the effects of Tp and Tb on plasma cholesterol and gut microbiota using hypercholesterolemic hamsters as a model. Male golden hamsters were randomly allocated to 6 groups fed one of the following 6 diets, namely, low-cholesterol diet (LCD), high-cholesterol diet (HCD), HCD + 0.5% Tp (LTp), HCD + 1% Tp (HTp), HCD + 0.5% Tb (LTb), and HCD + 1% Tb (HTb). Results showed that Tb administration at 1% could significantly reduce plasma total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDLC), and the ratio of non-HDLC to HDLC, whereas Tp supplementation had no effect. Mechanistically, Tb but not Tp could decrease plasma cholesterol by increasing the excretion of fecal bile acids via upregulating gene expression of cholesterol 7α-hydroxylase (CYP7A1) and liver X receptor alpha (LXRα). In addition, Tb supplementation at 1% could increase the gut microbiota diversity, reduce the ratio of Firmicutes/Bacteroidetes and favorably increase the abundance of beneficial microbial genera Bifidobacterium. In conclusion, dietary Tb supplementation was more effective than Tp in mitigating hypercholesterolemia by increasing the excretion of fecal bile acids and favorably modulating gut microbiota.