Calcineurin (CN) activation is a main cause of cancerous tumor formation, one of the leading causes of death globally. Cyclosporine-A (CsA) is a commercially available oral drug that inhibits CN activation; however, low bioavailability limits its use. Nine patented CsA conjugates are potential alternatives to CsA as they have improved cytotoxicities and bioavailabilities but unknown CN-binding affinity. This study aimed to identify the CN- inhibition strength and bioavailability of CsA conjugates in silico drug-likeness evaluation via modified Lipinski’s Rule of Five was done on CsA, voclosporin, and CsA conjugates to test bioavailability. The binding affinities of bioavailable compounds were computed via docking to CN in five trials, and the binding affinities were compared. The Water-soluble, RVal, IIA, Alpha, and MeBmt 2 conjugates showed improved bioavailabilities compared to CsA as they passed the drug-likeness screening. After five trials of computational docking to CN, the IIA and RVal conjugates showed improved binding affinities at -15.8 kcal/mol and -15.2 kcal/mol, respectively, compared to CsA at -14.3 kcal/mol. Notably, IIA also showed an improved binding affinity compared to voclosporin at -15.5 kcal/mol. These results suggest that CsA conjugates may be better oral chemotherapeutic drugs than CsA.