BACKGROUND: Huangjiu is an important component of traditional fermented food. It is produced by cereal fermentation. Sticky rice fermented huangjiu is an abundant source of polysaccharides, oligosaccharides, proteins, amino acids, and flavor compounds (POPAF), and it has been used as a dietary supplement and pharmaceutical ingredient. The purpose of this study is to explore the alleviation of constipation using sticky rice fermented huangjiu, with the aim of providing a basis for the nutritional treatment of constipation.RESULTS: Sticky rice fermented huangjiu was more effective in the alleviation of constipation than same concentration of ethanol treatment on serum neurotransmitters, gut microbiota, and intestinal metabolites in this 17 days constipation mouse model. Compared with ethanol treatment, the administration of sticky rice fermented huangjiu to constipated mice increased gastrointestinal motility. It alleviated the decrease in motilin (27.94%), substance P (13.85%), gastrin (63.46%), 5-hydroxytryptamine (4.55%), and short-chain fatty acid (19.80%) levels, and alleviated the increase in somatostatin levels (9.54%). Furthermore, the administration of sticky rice fermented huangjiu regulated the microbiota-mediated gut ecology through alterations in the characteristic taxa.CONCLUSION: The results reveal that sticky rice fermented huangjiu may alleviate loperamide-induced constipation by the regulation of serum neurotransmitters and gut microbiota. These findings reveal that huangjiu is endowed with many functional components by cereal fermentation, and the bioactive substances in huangjiu can be separated and applied for medical treatment or diet therapy in the future.