To explore the hepaprotective sesquiterpenes from Curcuma longa L., the Feature-Based Molecular Networking (FBMN) strategy was used to annotate the sesquiterpenes in the ethyl acetate fraction of C. longa (EAC) and their MS/MS fragmentation patterns. A total of 30 sesquiterpenes (1−30) were identified from the EAC based on ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) data. Network pharmacology and molecular docking elucidated procurcumenol (24) may targeted the key genes protein kinase B alpha (AKT1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) through regulating the PI3K/AKT signaling pathway in the prevention of alcoholic liver disease (ALD). Furthermore, compound 24, as the main constituent of EAC, exerted anti-inflammatory effects in ALD by downregulating inflammatory factors, such as TNF-α, IL-6. Western blotting analysis showed that it can up-regulate the phosphoinositol-3-kinase (p-PI3K) and p-AKT levels. Taken together, our findings suggested that 24 exerts therapeutic effects on ALD in NCTC1469 cells by suppressing inflammatory and modulating the PI3K/AKT signaling pathway.