We investigate the encapsulation of bovine serum albumin (BSA) in chemical-treated and chitosan-coated yeast cells, Saccharomyces cerevisiae (S. cerevisiae), for the controlled release of BSA. The chemical treatment can sufficiently enlarge the small-sized cell-wall cavities and/or break the integrity for the entrance of BSA to the interior of yeast cells, and the additional chitosan coating can well prevent the rapid release of encapsulated BSA from the yeast-derived microcapsules. The sodium hydroxide pretreated S. cerevisiae gives a maximum encapsulation yield of (10.1 ± 0.2)% for BSA. An additional coating of S. cerevisiae with chitosan can reduce the initial burst release of BSA and extend the release period from 24 h in the chitosan-free case to 48 h in phosphate buffer at pH 7.4. The prepared microcapsules can well keep the shapes and sizes of yeast cells and thus show uniform sizes of 3.85 ± 0.81 μm. The encapsulated BSA well retains its pristine ultraviolet spectroscopic and chromatographic behaviors. The present microencapsulation protocol has the advantages of convenient and mild operation, high encapsulation efficiency, and organic solvent-free nature, which is of reference value for establishing high-performance controllable biomacromolecule-delivery systems.