Background: Antioxidants derived from medicinal plants have the capacity to protect the liver from oxidative stress and exposure to chemicals. The current study is aimed at assessing the potential benefits of a plant-based treatment involving Swertia chirality (S. chirayita). Methods: Gas Chromatography-Mass Spectrometry (GC-MS) analysis was conducted to identify the chemical constituents of the experimental plants. The 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed to assess the cytotoxic activity of medicinal herbs on the HepG2 cell line. The antiproliferative activity of Swertia chirayita and the anticancer standard drug cisplatin was determined using Annexin V staining on a flow cytometer. The effectiveness of S. chirayita extracts as a hepatoprotectant was further evaluated in a Carbon tetrachloride (CCl₄)-induced rat model, while antioxidant activity was measured through Superoxide Dismutase (SOD), glutathione peroxidase (GPx), and Catalase (CAT) assays. An in silico study was carried out to assess the efficacy of ethanol extract of S. chirayita (ESC) and hexane extract of S. chirayita (HSC) on Transforming growth factor-beta (TGF-β) and Matrix metalloproteinase-8 (MMP-8) inflammatory markers. Results: The ESC extract exhibited the highest concentration of bioactive phytocompounds and displayed remarkable scavenging capabilities against 2,2-Diphenyl-1-picrylhydrazyl (DPPH), Nitric Oxide (NO), superoxide anion (O₂^-), and the reducing power assay compared to the HSC extract. The antimicrobial effects of the herbal extracts yielded superior results against bacterial pathogens. Additionally, the ESC extract demonstrated more potent cytotoxic and apoptotic activities against HepG2 cancer cells than the HSC extract and cisplatin, with fewer adverse effects on normal HEK-293 cells. Statistically significant differences (p < 0.05) were observed in various parameters. To further validate these results, liver function enzyme assays, stress indicators, and inflammatory biomarkers were employed. Histopathological examination of the liver revealed the protective effects of S. chirayita extracts and cisplatin, effectively mitigating and reversing hepatotoxicity. Furthermore, molecular docking, coupled with absorption, distribution, metabolism, excretion and toxicity (ADMET) profiling, identified the top five phytocompounds with anti-inflammatory potential against TGF-β and MMP-8 proteins, making them suitable targets for combating liver disease. Conclusions: S. chirayita extracts exhibit potent hepatoprotective activity attributed to the presence of significant phytocompounds. Their efficacy suggests their potential utilization as robust therapeutic agents in the pharmaceutical industry, validating the effectiveness of their ethnopharmacological properties.