BackgroundsPostmenopausal osteoporosis (PMO) is associated with dysregulation of bone metabolism and gut microbiota. Quinoa is a grain with high nutritional value, and its effects and potential mechanisms on PMO have not been reported yet. Therefore, the purpose of this study is to investigate the bone protective effect of quinoa on ovariectomy (OVX) rats by regulating bone metabolism and gut microbiota.ResultsQuinoa significantly improved osteoporosis‐related biochemical parameters of OVX rats,ameliorated ovariectomy‐induced bone density reduction and trabecular structure damage. And quinoa intervention may repair the intestinal barrier by upregulating the expression of tight junction proteins in the duodenum. In addition, quinoa increased the levels of Firmicutes and Bacteroidetes, and decreased the levels of Bacteroidetes and Prevotella, reversing the dysregulation of the gut microbiota. This may be related to Estrogen signaling pathway, Secondary and Primary bile acid biosynthesis, Benzoate degradation, Synthesis and degradation of ketone bodies, NOD‐like receptor signaling pathway, Biosynthesis of the tropane, piperidine, and pyridine alkaloids. The correlations analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and parameters related to osteoporosis.ConclusionQuinoa could significantly reverse the high intestinal permeability, change the composition of gut microbiota in OVX rats, thereby improving the bone microstructure deterioration and bone metabolism disorder, and ultimately protect the bone loss of OVX rats.This article is protected by copyright. All rights reserved.