Inflammation, while essential for host defense, becomes a driving force behind a wide spectrum of chronic disorders when dysregulated, including arthritis, cardiovascular diseases, metabolic syndrome, and neurodegeneration. Conventional anti-inflammatory therapies, though effective, are often constrained by adverse effects, drug resistance, and limited long-term safety, prompting a paradigm shift toward safer, multi-targeted natural interventions. In this context, Ocimum sanctum (Tulsi), an eminent medicinal herb in Ayurvedic medicine, has emerged as a promising candidate owing to its diverse bioactive profile and broad-spectrum pharmacological activities. This review presents a comprehensive synthesis of the phytochemistry of Ocimum sanctum with a particular emphasis on its enzyme-mediated anti-inflammatory mechanisms. Tulsi contains a rich array of phytoconstituents, including eugenol, ursolic acid, rosmarinic acid, apigenin, and other flavonoids and terpenoids, which collectively orchestrate its therapeutic effects. These compounds exert potent anti-inflammatory actions by targeting key enzymatic pathways such as cyclooxygenase (COX) and lipoxygenase (LOX), thereby attenuating the biosynthesis of pro-inflammatory mediators like prostaglandins and leukotrienes. Furthermore, Tulsi modulates intracellular signaling cascades, notably inhibiting nuclear factor-kappa B (NF-κB) activation, resulting in suppressed expression of inflammatory cytokines including TNF-α, IL-1β, and IL-6. Its strong antioxidant capacity further complements these effects by neutralizing reactive oxygen species and mitigating oxidative stress-induced tissue damage. Collectively, Ocimum sanctum represents a multi-mechanistic, plant-based anti-inflammatory agent with significant therapeutic promise. Future research should prioritize standardization, molecular-level validation, and well-designed clinical trials to facilitate its integration into evidence-based modern therapeutics.