Paracetamol (acetaminophen) is widely used as an analgesic and antipyretic; however, overdose results in hepatotoxicity primarily mediated through its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). This study aims to explore the hepatoprotective potential of selected phytochemicals—silymarin, piperine, quercetin, and gallic acid—through molecular docking against key proteins implicated in paracetamol-induced liver injury. In silico docking studies were performed using Schrödinger Release 2021-4 on a high-performance Ubuntu workstation. Ligands were sketched in Maestro, processed via LigPrep under OPLS_2005 force field conditions, and docked using Glide in XP mode. Seven protein targets were selected: succinate dehydrogenase (SDH), glutathione reductase (GSHR), cyclooxygenase-2 (Cox2), TNF-α, IL-6, IL-1β, and JNK, representing key pathways including mitochondrial dysfunction, oxidative stress, and inflammation. The results revealed that quercetin exhibited the strongest binding affinities across all targets, with a notable docking score of –9.060 for JNK and –8.027 for IL-1β, suggesting potent anti-inflammatory and mitochondrial protective roles. Gallic acid demonstrated broad-spectrum efficacy, especially against GSHR (–5.288) and JNK (–8.052), implicating its antioxidant potential. Silymarin showed significant binding to Cox2 (–7.073) and SDH (–5.665), supporting its known hepatoprotective effect. Piperine, while moderate in most targets, showed enhanced affinity for Cox2 (–6.608), indicating anti-inflammatory relevance. Overall, the study highlights quercetin and gallic acid as promising phytochemicals that may counteract paracetamol-induced hepatotoxicity by targeting multiple pathophysiological proteins. Further in vitro and in vivo validations are warranted to establish their therapeutic potential.