This study investigates the suppression of ZrCr2 formation at the Cr/Zr interface by introducing trace amounts of Mg, Zn, and Sn into Cr coatings. Combining the first-principles calculation and experimental analyses, the inhibitory effects of these dopants on ZrCr2 are examined. First-principles calculations predicted that Zn, Mg, and Sn can elevate the formation energy of ZrCr2, with Mg exhibiting the most significant effect, thereby exerting an inhibitory influence on ZrCr2 formation. Experimental findings demonstrate that Sn notably inhibits ZrCr2 formation, resulting in a reduction of ZrCr2 approximately 10%. However, Zn and Mg do not exhibit a substantial inhibitory effect on ZrCr2 due to their low yield resulting from the low vaporization temperature. These results from computational simulations, alongside experimental validations, underscore promising strategies for mitigating ZrCr2 formation, offering valuable insights for enhancing performance in nuclear fuel cladding applications.