Calotropis gigantea commonly known as ‘Shweta Arka’ is a highly medicinal drought resistant. Plant contains milky latex in the stem which is used as an antidote for snake poison in dried form. Whereas, dried leaves of the Calotropis plant are used as an expectorant and anti- inflammatory for the cure of paralysis and rheumatic pains. It contains pesticidal, insecticidal, fungicidal, anti-bacterial properties. The plant has been reported to be effective in more than hundred human diseases. Various bioactive compounds have been extracted from C. gigantea fruit follicle. Present investigation deals with the determination of bioactive constituents from the leaf of C. gigantea using LCMS and their comparative analysis. The LCMS analysis revealed the presence of total 22 bioactive compounds with valuable activity. Most of the compounds were found to be similar leaf and latex, but small variation was also observed in their chemical profile. The Compounds identified from the fruit follicle of C. gigantea were Cycloalliin, 1-(4-Hydroxy-2-methylpyrimid-5-ylmethyl)-3-(beta-hydroxyethyl) --2-methylpyridinium, 2- Dodecylbenzenesulfonic acid, Rimocidine, Sarcostin, Mycinamicin IV, Lycoperoside D etc. whereas the rest of the compounds were similar in both leaf and latex.