Background: Amphotericin B is a gold-standard drug, particularly for the treatment of systemic fungal infections. However, its low solubility and permeability limit its application. To improve its bioavailability, AmB may be conjugated with various water-soluble auxiliary groups. Methods: Custom R group Enumeration was used at the designated sites of Amphotericin B. The designated sites taken into consideration are the carboxyl moiety of the aglycone part and the amine moiety of the glycone part of Amphotericin B for Enumeration purposes. The enumerated molecules were subjected to QikProp properties. Results: We identified fourteen hits with improved predicted aqueous solubility and cell permeability. Conclusion: Enumeration might be applicable in improving bioavailability, which could lead to the oral formulation of the Amphotericin B drug.