People's health is adversely impacted by diseases caused by abnormal inflammation; therefore, more effective treatments as well as research into the underlying mechanisms are urgently required. According to our preliminary research, geniposidic acid exhibits anti-inflammatory properties. Even though geniposidic acid has been linked to inflammation and shows promise in the treatment of aberrant inflammatory illnesses, its exact antiinflammatory mechanism is unknown. To create in vitro cellular inflammatory models for 48 h, we employed THP-1 cells treated with PMA (phorbol 12-myristate 13-acetate) and LPS (lipopolysaccharide), which were then treated with geniposidic acid. These models were further validated by ELISA-based detection of the expression of the interleukins IL-1, IL-6, IL-8, and tumor necrosis factor TNF-α. The anti-inflammatory properties of geniposidic acid were investigated using proteomics based on TMT-LC-MS/MS analysis and bioinformatic analysis. Geniposidic acid can act as an anti-inflammatory agent in inflammatory cell models, according to the successfully established THP-1 cell inflammatory models. GO and KEGG analyses further established numerous bioprocesses, molecular activities, and signaling pathways related to the regulation of geniposidic acid. Additionally, western blot analysis confirmed that geniposidic acid can suppress inflammation by lowering the expression of proteins linked to inflammation such as CXCL10, PPM1H, and TLR5. After more thorough mechanistic, animal, and clinical research were included, the current study revealed that anti-inflammatory efficacy of geniposidic acid from the standpoint of proteomics made it a promising medicine to cure and prevent diseases caused by aberrant inflammation.