This research explores the anti-inflammatory effects of Nordihydroguaiaretic Acid (NDGA), derived from the Creosote Bush (Larrea tridentata), in comparison to Zileuton, a synthetic inhibitor of leukotriene biosynthesis. The investigation employs molecular docking techniques alongside ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis. Inflammation, an essential immune mechanism, is significantly influenced by leukotrienes via the lipoxygenase pathway. Both NDGA and Zileuton target this pathway, with NDGA acting as an inhibitor of 5-lipoxygenase and Zileuton preventing leukotriene synthesis. Molecular docking studies demonstrated robust binding affinities for both compounds, with NDGA achieving a binding energy of -7.1 kcal/mol and Zileuton slightly stronger at -7.6 kcal/mol. ADMET profiling revealed that NDGA exhibited superior pharmacokinetics and reduced toxicity in comparison to Zileuton. Additionally, NDGA showed favorable physicochemical properties, including improved solubility, optimal lipophilicity, and enhanced bioavailability, highlighting its potential in medicinal chemistry. These findings indicate that NDGA might be a viable natural alternative to synthetic options like Zileuton for the treatment of inflammation-associated conditions.