During the last decades, many of the poorly controlled diseases were treated using newly developed peptide and proteins. Although the majority of such therapeutic moieties have undesirable pharmacokinetic properties and there is still need for administration in relatively short intervals, new formulation strategies allow us to select appropriate carriers in the development of these compounds. Polyesters such as polylactide-co-glycolide were used to stabilize and control the release rate of peptide and proteins. Besides many appropriate characteristics, these polymers, however, have some limitations and drawbacks which limit their extensive use in formulation. In this review, the factors affecting the loading, release behavior, particle size distribution and burst effect were evaluated and appropriate suggestions to optimize the formulation with these polymers were proposed.