We discussed the molecular coping mechanism of quinoa in flooding environment, and we analyzed the transcriptome in quinoa during flooding stress to identify key genes involved in these stress responses. Then, we examined the metabolome to determine how genetic changes cause metabolic adaptations. We found that several genes and their corresponding metabolites are altered in three quinoa strains. Our results may provide a basis for breeding and identifying quinoa flood-resistant varieties. Identifying these genetic and metabolic changes will allow improve husbandry and will allow quinoa to be grown in various environments.