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Here, we report a Lys\u2010C protease\u2010cleavable solubilizing tag and its use to synthesize difficult\u2010to\u2010obtain D\u2010proteins. Our tag is easily installed onto multiple amino acids such as <jats:sup>D<\/jats:sup>Lys, <jats:sup>D<\/jats:sup>Ser, <jats:sup>D<\/jats:sup>Thr, and\/or the N\u2010terminal amino acid of hydrophobic D\u2010peptides, is impervious to various reaction conditions, such as peptide synthesis, ligation, desulfurization, and transition metal\u2010mediated deprotection, and yet can be completely removed by Lys\u2010C protease under denaturing conditions to give the desired D\u2010protein. The efficacy and practicality of the new method were exemplified in the synthesis of two challenging D\u2010proteins: D\u2010enantiomers of programmed cell death protein 1 IgV domain and SARS\u2010CoV\u20102 envelope protein, in high yield. 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