Periostin plays a crucial role in fibrosis, which is involved in kidney aging. A few studies have shown that lipid metabolism is involved in kidney aging. We investigated the role of periostin in lipid metabolism during kidney aging. Renal function, fibrosis, and inflammatory markers were studied using urine, blood, and tissue samples from wild-type (WT) C57BL/6 mice and Postn-null mice of 2 and 24 months of age. Lipids were quantitatively profiled using liquid chromatography-tandem mass spectrometry in the multiple reaction monitoring mode. Renal function was worse and tubular atrophy/interstitial fibrosis, periostin expression, and inflammatory and fibrotic markers were more severe in aged WT mice than in young WT mice. In aged Postn-null mice, these changes were mitigated. Thirty-five differentially regulated lipids were identified. Phosphatidylcholines, cholesteryl ester, cholesterol, ceramide-1-phosphate, and CCL5 expression were significantly higher in aged WT mice than in aged Postn-null mice. Particularly, linoleic acid, linolenic acid, arachidonic acid, and docosahexaenoic acid differed strongly between the two groups. Lysophosphatidylcholine acyltransferase 2, which converts lysophosphatidylcholine to phosphatidylcholine, was significantly higher in aged WT mice than in aged Postn-null mice. Periostin expression in the kidneys increased with age, and periostin ablation delayed aging. Changes in lipids and their metabolism were found in Postn-null mice. Further research on the precise mechanisms of and relationships between lipid expression and metabolism, kidney aging, and periostin expression is warranted.