Cross-linking two cysteine residues to give a helix-constrained cyclic peptide confers drug-like properties such as cell uptake and enzymatic resistance. This cross-linking approach, also known as bis-thioether stapling (BTS), therefore constitutes an attractive chemical tool in biomedical research. However, current protocols for BTS with saturated dihaloalkanes relies on alkylation under basic conditions which remains sluggish and may lead to disulfide formation, beta-elimination and undesired alkylation of other nucleophilic side chains. Therefore, a non-basic protocol to mediate BTS is highly desirable. We present a Zn(II)-catalyzed BTS protocol performed under weakly acidic conditions. The reaction is performed in aqueous-organic solvent mixtures and the catalyst, Zn(OAc)2, is widely available and non-toxic. The protocol was used to synthesize a bis-thioether stapled peptide inhibitor of the therapeutically relevant p53/HDM2 and p53/HDMX protein-protein interactions.