In this chapter, the design, synthesis and properties of synthetic molecules for protein manipulations are described. Structural modification of poly(ethylene glycol) (PEG) to change the topology and to add amphiphilicity affords protein stabilization effects. Macrocyclization of PEG with pentaerythritol corners leads to different properties in hydrophobicity and thermal responses from the corresponding linear PEGs. The topological effects afford the macrocyclic PEGs with functions to interact with thermally denatured proteins to suppress aggregation. Amphiphilic modification of PEGs with an aromatic group is also effective for protein aggregation suppression. Particularly, relatively short PEGs can be functionalized for protein manipulation by the amphiphilic modification. Folding of a polypeptide chain into the native structure is an important process of a protein to perform its biological function, and the folding process is promoted by chaperons in cells. Development of synthetic promotors for oxidative protein folding is described in the last part of this chapter.