Protein-coated microbubbles have become one of the emerging platforms in biomedical research as theranostic agents. In recent years, microbubbles have been extensively used as ultrasound contrast agents and carriers of molecular cargoes, pertaining to which several studies have focused on tuning the properties of these bubbles to achieve a higher degree of biocompatibility and extended stability. Synthesis of microbubbles has so far been traditionally carried out with pre-heated proteins like bovine serum albumin (BSA) as shell coatings, owing to the ease in making BSA crosslinked structures through disulfide bridge formation. We, however, have performed experiments to demonstrate that air core microbubbles formed with native BSA are more stable compared with those formed using denatured BSA. The experimental observations have been supported with analytical modeling and computational studies, which offer insights into the effect of BSA conformation in stabilizing the microbubbles shells and prolonging their lifetimes.