Background: Treatment for hepatic complications still remains a challenging issue for healthcare professionals due to lack of multitargeted and biomolecular-based therapeutic approaches. Moreover, contemporary therapeutic approaches often fail to achieve widespread and sustained utilization due to limitations related to affordability, accessibility and availability. Terminalia arjuna (Roxb. ex DC.) Wight & Arn., a well-known Indian medicinal plant, is recognized for its antioxidant, anti-inflammatory, and cardioprotective properties. Objectives: This study aims to explore the metabolomic profiling (HPTLC and LC-MS) and network pharmacology–based biomolecular targets of T. arjuna in the treatment of hepatic disease. Methodology: Pharmacopoeial assessment was conducted to establish quality standards, and DPPH antioxidant activity was analyzed to evaluate free radical scavenging. Phytochemical insights and biomolecular approaches were revealed through HPTLC and LC-MS technique and network pharmacology analysis. Network pharmacology and gene ontology analyses further examined the plant’s multitargeted effects on hepatic disorders. Results: The results confirmed that T. arjuna meets pharmacopoeial quality standards, with notable DPPH radical scavenging activity (IC₅₀ = 182.2 ± 1.846 μg/mL). Metabolomic analysis revealed significant marker compounds, while network pharmacology identified TP53, IL6, and HFE as primary targets interacting with gallic acid, ellagic acid, arjunolic acid, procyanidin, and catechin. These interactions regulate liver carcinoma, hepatocellular carcinoma risk, hypogammaglobulinemia, and liver cirrhosis. Conclusion: The study concludes that T. arjuna effectively modulates TP53, IL6, and HFE expression, providing a promising natural approach for liver disorders. However, further preclinical and clinical studies are needed to bridge existing scientific gaps and validate its therapeutic efficacy.