Proteins fold in a confined space not only in vivo, i.e., folding assisted by molecular chaperons and chaperonins in a crowded cellular medium, but also in vitro as in production of recombinant proteins. Despite extensive work on protein folding in bulk, little is known about how and to what extent the thermodynamics and kinetics of protein folding are altered by confinement. In this presentation, we use a Go-like off-lattice model to investigate the folding and stability of an all β-sheet protein in both spherical cages of different sizes and surface hydrophobicity and surfactant/polymer assemblies. Our presentation is started with brief introduction of complexity of protein in vivo, and then presented the models and simulation methods on how to solve this complex system. According to the simulation results, we find that whereas extreme confinement inhibits correct folding, a hydrophilic confine stabilizes the protein due to restriction of the unfolded configurations. In a hydrophobic confinement, however, strong attraction from the cage surface destabilizes the confined protein because of competition between self-aggregation and adsorption of hydrophobic residues. We show that the kinetics of protein collapse and folding is strongly correlated with both the cage size and the surface hydrophobicity. It is demonstrated that a cage of moderate size and hydrophobicity optimizes both the folding yield and kinetics of structural transitions. To support the simulation results, we have also investigated the refolding of proteins in the presence of folding aids, such surfactant CTAB, PNIPAAm and DGP, to provide an effective confinement of the proteins. It is shown that, as predicted by coarse-grained simulations, folding aids at different status can facilitate the collapse of denatured protein and promote the conformational rearrangement and thereby gives an improved recovery of protein activity.