Abstract <p>The leaves of <i>Vaccinium bracteatum</i> Thunb. (VBTL) are an important natural treasure trove of raw materials to produce healthy foods, and the active compounds in VBTL play a key role. However, there has been a lack of systematic studies on the active compounds of VBTL throughout different periods. In this study, we investigated the changes in the active compounds of VBTL during three vital times: mid-spring in April, late spring in May, and early summer in June. We use proteomics and metabolomics to reveal the development of its nutritional and therapeutic aspects. The results showed that the abundance of proteins in the phenylpropanoid and flavonoid biosynthesis pathways was generally higher during the mid-spring stage. In contrast, flavonoids, which form the bitter and astringent flavor of tea, were lower, contributing to the production of VBTL-derived tea. The iridoid and iridoid glycosides associated with “wu-mi” staining were higher in late spring. VBTL were most resistant to oxidative stress in early summer. The abundance of proteins related to glutathione redox regulation and reactive oxygen species scavenging was higher at this stage. By studying the VBTL throughout three distinct periods, we can better understand the fluctuating properties of its active components. This study provides a solid foundation for determining the most advantageous moment for harvesting and maximizing its nutritional value.</p>