Royal jelly (RJ) is rich in various nutrients with multiple health-promoting properties. This study aims to evaluate whether RJ can modulate related metabolite in the natural aging mice. Male C57BL/6J mice drank RJ solution daily for 9 months. Determination of serum lipids and pathological analysis exhibited that triglycerides (TG), serum cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were decreased by 31.15%, 9.96%, and 22.58%, respectively, the morphology of brain nerve cells was also effectively recovered after RJ intervention. Lipidomic analysis showed that RJ could improve the levels of different kinds of lipids in aging mice brain, especially by increasing the content of antioxidant ether ester, and that the ratio of monounsaturated fatty acid (MUFA) to polyunsaturated fatty acid (PUFA) was up by 23.46%, which could alleviate oxidative stress. Moreover, the metabolism of glycerol phospholipids, glycerols, and fatty acids in aging mice could be regulated by RJ. RJ intervention can effectively improve lipid metabolism disorders caused by aging.