Mume Fructus (MF), a representative substance in the field of medicine-food homology, has been extensively utilized in clinical treatments and daily diets for its raw and processed forms. This study aimed to establish the spectrum-effect relationship between ultra-high-performance liquid chromatography coupled with quadrupole tandem time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) fingerprints and anti-inflammatory and antitussive activities of raw and processed MF extracts. In UHPLC-Q-TOF-MS/MS fingerprints, a total of 21 common peaks were identified. Bioactivity assays demonstrated that the raw and processed MF extracts exhibited varying degrees of anti-inflammatory and antitussive effects. Subsequently, the relevant pharmacologically active ingredients were screened by grey relation analysis and partial least squares regression. The results showed that nine components were associated with anti-inflammatory effects, namely, citric acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, fumaric acid, gallic acid, neochlorogenic acid, chlorogenic acid, and ononin. Additionally, three components were linked to antitussive activity: amygdalin, syringic acid, and succinic acid, respectively. This work developed a model combining UHPLC-Q-TOF-MS/MS fingerprints with anti-inflammatory and antitussive activities to study the spectrum-effect relationship of raw and processed MF extracts. The findings provide a reference for the discovery of bioactive components and contribute to the clinical rationalization of medications.