The Chikungunya virus (CHIKV) is an alphavirus transmitted to humans by the Aedes mosquitoes surrounding the tropical and subtropical regions of the world. Transmission was first detected in 1952, and there have been ongoing outbreaks in the Indian Ocean from 2007. The CHIKV disease is characterized by an abrupt onset of fevers, headaches, chronic and severe musculoskeletal pain. There are few data on the specific inhibition of CHIKV activity. Therefore, our research aims to inhibit the non-structural protein-2 protease (nsP2pro), which is mediated by a cysteine-histidine dyad1. Preliminary data on the inhibition of CHIKVnsP2pro have proven to be challenging. Through literature investigation and in silico modelling we designed covalent peptide inhibitors and aim to synthesise dipeptides incorporating reactive functional groups (warheads), including aldehyde, α-ketoamide, and nitrile substituents that irreversibly bind at the active site. Macrocyclic peptides cyclised via a thiazoline motif will also be explored as an alternative strategy to prepare peptidomimetic inhibitors for CHIKV nsP2pro. Our research will highlight the efforts towards synthesizing peptidomimetics to inhibit the challenging protease. The nsP2pro enzyme is also highly conserved among alphaviruses, providing opportunities for broad-spectrum inhibitors that may be active against other alphaviruses. The ongoing pandemic should bring awareness to the dangers of neglected viruses in third-world countries that could bring harm to our communities.