The high demand of novel peptide and peptidomimetics based on the amount of genomic and proteomic data need be matched by synthesis and screening. The design and synthesis of peptide and peptidomimetics are so important because the peptide and protein-protein interaction play a key role in molecule recognition and signaling. The modified peptides have better stability and pharmacokinetic properties which may be guided by rational design and molecular modeling. Now many organic and medicinal chemists have chosen peptide and peptidomimetics as potential drug candidates for many targets. In this dissertation, research efforts in design and synthesis of cyclic peptides with stabilized secondary structure have been investigated. Cyclization of linear peptides may restrict the number of available conformations which may improve the affinity attaching to the target. In this study, different beta turn linkers have been designed and synthesized to achieve more stable cyclic peptides with beta-sheet structures. Based on different beta turn linkers, analogs of cyclic peptides have been synthesized and screened. The structure activity relationships (SAR) of these cyclic peptide analogs have been studied. In chapter three, analogs of peptidomimetic inhibitors have been designed and synthesized. These peptide analogs are targetingHuman Rhinovirus (HRV) and Coronavirus (CoV) by inhibiting the cysteine protease. The docking and modeling studies have been shown. The structures of this kind of inhibitors include five fragments. The warhead provides the activity, which can covalently react with the thiol of cysteine protease and permanently eliminate its proteolytic activity. The warhead is linked to a peptide backbone including the other four parts that are designed to position the warhead where it can specially react with the critical thiol of the cysteine protease active site. The side chain of each amino acid has been optimized to achieve better solubility and permeability. We successfully synthesized some compounds with good potency.