Protein stability is a major challenge to overcome during manufacturing, upstream and downstream processes, formulation, transportation and storage of biopharmaceuticals. Proteins may aggregate during these activities in addition to chemical changes. Aggregation is often irreversible leading to inactive and potentially immunogenic species, resulting in to reduced efficacy and toxicity to patients. Formulation development involves selection of appropriate excipients to stabilize the protein drugs throughout its recommended shelf life against potential excursions in its life cycle and aid in the delivery of therapeutics into the patient. While role of many excipients in the stability of formulation is well documented, scares information is available on role of Cyclodextrins in stabilization of therapeutic proteins such mAbs. Cyclodextrins play a vital role in reduction of interfacial tension with the environment and hydrophobic interactions among the protein molecules. In the present study stabilizing effects of novel Cyclodextrins, KLEPTOSE® HPB and HP in various therapeutics protein formulations have been investigated. Physical-chemical stability was influenced under different stress conditions such as thermal and agitation for monoclonal antibodies and human growth hormone. We employed a two-prong approach, high throughput screening and conventional chromatographic methods to establish validation. This study provides insight in to both methodologies to understand interplay between protein and surrounding environments. We attempt to provide role of novel Cyclodextrins to reduce aggregation and develop therapeutically effective and safe protein formulations.