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BACKGROUND Time-restricted feeding (TRF) is an effective means that can efficiently administer the metabolism and health of animal and humans. However, the effect of TRF on hypothalamic function remains unclear yet. RESULTS Results showed that TRF significantly increased the activities of digestive enzymes lipase, maltase in the duodenum and lipase, trypsin in the pancreas whereas significantly decreased serum gastrointestinal hormones gastrin, GLP-1, CCK, PYY, and ghrelin. Amino acid metabolism-related metabolites including citrulline, kynurenine, N-acetylleucine, L-tryptophan, and L-tyrosine significantly increased in TRF group. Differential metabolites were mainly enriched in phenylalanine, tyrosine and tryptophan biosynthesis and tryptophan metabolism. Transcriptomic analysis of hypothalamus showed that a total of 462 DEGs was significantly changed by TRF. Specially, DEGs involved in aromatic amino acid metabolism pathways such as DDC, TH, GOT2, and DBH were significantly down-regulated whereas the expression of CYP1B1 was significantly up-regulated. Moreover, DEGs (PDYN and PPP3CA) involved in amphetamine addiction, and cocaine addiction were also down-regulated in the TRF group. CONCLUSION Taken together, these results suggested that TRF improved the digestion and absorption of nutrients and thus increased the accessibilities of aromatic amino acids. The increasing of circulating aromatic amino acids might mediate the regulatory neuroendocrine effects of TRF regimes on the hypothalamus functions especially on drug addictions. This study reveals a possible mechanism underlying the effects of regulating feeding patterns on the function of the hypothalamus by altering aromatic amino acids metabolism. This article is protected by copyright. All rights reserved.