Pathogenic species of Leptospira cause leptospirosis, a global zoonotic disease. Leptospirosis continues to have major impacts on people of developing countries with inestimable morbidity and mortality. Leptospira outer membrane proteins (OMPs) may elicit tubular injury and inflammation through Toll-like receptor dependent pathway followed by activation of nuclear transcription factor kappa B (NF-kB) and mitogenactivated protein kinases (MAPK) and a differential induction of chemokines and cytokines relevant to tubular inflammation. The drugs available for this disease have shown no successful result, so in this work we aim at discovering natural and synthetic products as new leads in pharmaceutical development using many commercial softwares such as Accelrys Discovery Studio 3.5, Biosolve-IT and GOLD 5.1 suite for the molecular docking studies. For this, 50 natural and 50 synthetic compounds having anti-cancerous, anti-inflammatory, anti-microbial activity were derived from research articles and databases. Then by the docking results, comparative analyses between the natural and synthetic compounds were made to find the best compound among them. By the study, the natural compounds Sodium curcuminate and curcumin which belongs to same family of curcuma longa as well as Gemichalcone_B are the probable compounds for leptospirosis.