Protothecosis, a zoonotic algal infection needs to be addressed under the one health principles. Treatment of algal infections has always been a challenge. There is no specific treatment for protothecosis both in humans and animals. Currently the only treatment for humans and food animals are antifungals which is associated with risk of toxicity and emergence of resistance. This study was aimed at identifying compounds for the control of Protothecosis by conducting insilico analysis against sterol 14α-demethylase (CYP51/ERG11), a key enzyme involved in the biosynthesis of ergosterol in Prototheca Spp. Traditional Chinese Medicine (TCM) library present in Drugrep was used for selecting the top hits and the ligands were ranked based on predicted affinity and molecular dynamics (MD) simulations was conducted using GROMACS2021 package for a timescale of 30ns. Based on autodock Vina affinity score/X-Score Binding energy of six compounds from Drugrep, that scored above -9.0 Kcal/mol and did not violate Lipinski’s rule of five criteria were selected: Peimisine, Limonin, Hecogenin, Jervine,((25R)-Spirost-4-ene-3,12-dione), Cyclopamine and Obacunone. The MD results showed that the (25R)-Spirost-4-ene-3,12-dione) had the most stable root mean square deviation (RMSD) when bound to sterol 14α-demethylase. However, the root mean square fluctuation (RMSF) of the protein both in bound and unbound state was similar. Ligands Hecogenin and (25R)-Spirost-4-ene-3,12-dione) that had 3-4 and 1 hydrogen bonds, respectively showed fewer fluctuations as compared to others. These two predicted compounds the (25R)-Spirost-4-ene-3,12-dione) and Hecogenin could possibly be expanded for their potential as drug candidates against Prototheca spp.