Root rot disease poses a devastating threat to Coptis chinensis Franch, a medicinal plant prized for its bioactive alkaloids. To dissect its defense mechanisms, we conducted integrated transcriptomic and metabolomic analyses on resistant (R), early-stage infected (S-ES), and late-stage infected (S-LS) plants Our findings reveal a disease severity-dependent escalation in flavonoid metabolism. Key metabolites, such as kaempferol and quercetin derivatives, were significantly increased compared to R, paralleled by progressive upregulation of biosynthetic genes (PAL, CHS, CHI, FLS). Strikingly, salicylic acid (SA)-associated metabolites and pathway genes (NPR1, NPR3/NPR4) showed no differential expression across groups, contrasting with typical SA-mediated defenses in other species. This study uncovers flavonoid biosynthesis as the primary defense strategy in C. chinensis during root rot progression, while SA signaling may not be the main defense mechanism. These results provide actionable targets for enhancing disease resistance in medicinal plants through metabolic engineering.