Background: :Currently, clinically used drugs for internal fungal infections have severe side effects. Patients suffering from severe fungal infections and those at a constant risk of developing such infections require long-term administration of safe antifungals.Objective: :This work deals with the design and development of safe, non-toxic antifungals derived from natural compounds for immune-compromised patients, such as HIV patients, who are at a constant risk of developing internal fungal infections.Methods: :Molecular modeling, docking and molecular dynamics simulation studies were performed on the main constituents of ginger and their derivatives to study their capability to inhibit 14α- demethylase enzyme.Results: :Ergosterol is the key component of the fungal cell membrane for its integrity and rigidity, synthesized from lanosterol catalyzed by 14α-demethylase enzyme. In our studies, it is determined that 6-gingerol, 6-paradol, 6-shogaol and their imidazole and triazole derivatives can inhibit the synthesis of ergosterol thus weakening the fungal cell membranes. The triazole derivative of 6-gingerol forms enhanced binding interactions with the active site residues of 14α-demethylase, carries an affinity for catalytically required cofactor heme and forms a stable complex with time without the probability of premature expulsion. Thus, this compound inhibits the formation of ergosterol leading to weakened fungal cell membranes and eventually death of fungal cells.Conclusion: :The triazole derivative of 6-gingerol is recommended as a lead compound for the development of non-toxic antifungals.