Since last century, peptides have emerged as potential drugs with >90 FDA approvals for various targets with several in the pipeline. Sulphur, in peptides is present either as thiol (-SH) from Cys or thioether from Met. In this review, all the peptides approved by FDA since 2000 containing sulphur have been included. Among them ∼50 % contains disulphide bridges. This clearly demonstrates the significance of disulphide bonds in peptide drugs. This can be achieved synthetically by using orthogonal protecting groups (PGs) for –SH. These PGs are compatible with Solid Phase Peptide Synthesis (SPPS), which is still the method of choice for peptide synthesis. The orthogonal PGs used for Cys thiol side chain protecting for disulphide bond formation have been included which are currently in use both by academia and industry from small scale to large scale synthesis. In addition, the details of the FDA approved drugs containing Cys and Met (or both) have also been discussed. Display omitted •50 % of FDA approved peptides containing sulphur.•Total 26 peptide drugs have been approved since 2000 which contains sulphur as disulphide, thioether and thiophene.•Toolkit of cysteine orthogonal protecting groups used in Peptide Synthesis.•ADCs bioconjugation with linker is via thiol which comes from Cys of antibody.