Atherosclerosis, a leading cause of cardiovascular and cerebrovascular diseases, develops when macrophages accumulate oxidized low-density lipoprotein (LDL) and form foam cells in the arterial walls. High-density lipoprotein (HDL) exhibits anti-atherosclerotic functions via reverse cholesterol transport (RCT) from macrophages to the liver and cholesterol efflux in macrophages. HDL cholesterol efflux is mediated by cholesterol transport proteins, such as ATP-binding cassette transporter (ABC) A1, ABCG1, and scavenger receptor class B type I (SR-BI). Recent studies have investigated the potential of various food factors to enhance high-density lipoprotein (HDL) function. Caffeic acid and ferulic acid in coffee polyphenols promote RCT and cholesterol efflux by increasing the expression of ABCA1 and ABCG1 in macrophages. Resveratrol, hesperetin, and cyanidin-3-O-glucoside also exhibited similar effects. Xanthohumol, a hop polyphenol, activates RCT by increasing the activity of LCAT, a cholesterol esterification enzyme, leading to changes in HDL composition. Additionally, inhibitors of the small-intestinal cholesterol transporter NPC1L1 (Niemann-Pick C1 Like 1), such as ezetimibe, may promote RCT by decreasing the reabsorption of bile-derived cholesterol. At present, no studies have examined the usefulness of food factors in improving HDL function in humans. In the future, it is expected that the anti-atherosclerotic effect of food factors will be proven in terms of both the quantity and quality of HDL through randomized controlled trials based on strict protocols, including studies of side effects.