Melatonin has been suggested to play important roles in lipid metabolism as well as circadian rhythm; however, very few studies explored the effects of ramelteon, a selective melatonin receptor agonist, on serum lipid profiles. In this study effects of ramelteon on serum lipid profiles were explored, comparing to those of other sleep-promoting drugs including benzodiazepines and non-benzodiazepines, in patients with insomnia. We retrospectively reviewed medical charts of outpatients who were treated with ramelteon (8 mg/d) or other sleep-promoting drugs for no less than 8 weeks during the period between October 1st, 2011 and September 30th, 2014, and compared the changes in serum lipid profiles between the two groups. Patients with regular dialysis or malignant diseases treated with cytotoxic anti-cancer drugs, or whose lipid-lowering drugs were altered during the study period, were excluded. Among 365 or 855 outpatients treated with ramelteon or other sleep-promoting drugs, 35 or 46 patients, respectively, had complete serum low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) data. Serum LDL-C was significantly reduced from 103.1±4.4 to 94.6±4.2 mg/dL (8.2% reduction, p <0.05, n =31) in the ramelteon group, and was not significantly changed ( p =0.23, n =40) in the other sleep-promoting drug group. Non-HDL-C was significantly decreased from 138.8±6.0 to 130.6±4.9 mg/dL (5.9% reduction, p <0.05, n =32) in the ramelteon group, and was not significantly altered ( p =0.29, n =42) in the other sleep-promoting drug group. Ramelteon, but not other sleep-promoting drugs, specifically lowers serum LDL-C and non-HDL-C levels.