Objective: This study aimed to analyze differentially proteins at various growth stages of Dendrobium nobile Lindl and attempt to find some possible functional proteins related to plant growth or pharmacological activity. Methods: The samples were grouped into two categories based on their growth periods as 2-3 years (S1) and 7-8 years (S2), respectively. Tandem Mass Tag(TMT) labeling-based quantitative proteomics combined LC-MS/MS was applied to identify differential protein expression at various growth stages of Dendrobium nobile Lindl. Those proteins were analyzed by various bioinformatics methods. The activities of several antioxidant enzymes including superoxide dismutase(SOD), peroxidase (POD) and catalase (CAT) in the plant were specifically examined using commercially available assay kits. Results: A total of 6,032 proteins were identified with 283 differential proteins related to 168 up-regulated and 115 down-regulated. KEGG pathway enrichment analysis revealed that proteins involved in heat shock response, phenylpropanoid biosynthesis, and antioxidant activity showed significant changes across the growth stages. Specifically, a decrease in small heat shock proteins (sHSPs) was observed in older plants, potentially reducing their stress resilience, while proteins involved in lignin biosynthesis, such as SOD, CAT, and POD, were upregulated, suggesting improved stress response.