Polygonatum odoratum (MILL.) DRUCE is rich in bioactive components with high medicinal value. To maximize the clinical benefits, it is of great significance to efficiently extract key bioactive components from appropriate growth stages in which they are most abundant. In this study, we analyzed the changes of metabolite accumulation and protein expression in P. odoratum rhizomes at different growth stages using targeted metabolomics combined with proteomics, and identified a total of 1,237 differentially abundant metabolites (DAMs). Flavonoids accumulated most in winter, and the biosynthesis pathways associated with flavonoids, isoflavonoids, flavones and flavonols exhibited significant differentially expressed proteins (DEPs). Among them, PGT, FLS, CYP75B1, HIDH, IF7MAT, and UFT73C6 were positively correlated with flavonoid accumulation. Steroid saponins accumulated most in spring, and the biosynthetic pathways of steroid and brassinosteroid biosynthesis exhibited DEPs. Among them, FDFT1, TM7SF2, DHCR7, CAS1