This study compares the chemical composition, antioxidant effect, and anti-inflammatory potential of different parts (whole, flesh, and peels) of Codonopsis lanceolata roots (CLR). Component analysis performed using liquid chromatography (LC) revealed that the contents of vitamin B2, B3, tangshenoside I, lobetyolin, lancemaside A, and total polyphenol were highest in the CLR peels. Moreover, the peels also showed the highest antioxidant activity. All components of the CLR inhibited oxidative stress and enhanced mitochondrial biogenesis in LPS-treated RAW 264.7 cells, as quantified using fluorescent probes. Results of the Griess assay and enzyme-linked immunosorb ent assay, revealed that exposure to CLR suppressed the production of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines. CLR treatment also reduced the expression levels of cyclooxygenase-2 and inducible nitric oxide synthase protein through the regulation of nuclear factor-κB and mitogen-activated protein kinase signaling pathways, respectively, as determined by western blot. The findings of this study suggested that the CLR peels have a higher concentration of bioactive compounds than the amounts obtained in the flesh tissues of CLR. Thus, we propose that consuming CLR with the peel is more beneficial to the human body, than eating peeled.