Methods of making increased amounts of diketopiperazines (DKP) such as DA- DKP in pharmaceutical compositions of proteins and peptides are disclosed. The disclosure further provides methods of making a DKP, including (1) contacting albumin with an enzyme (such as a dipeptidyl peptidase IV (DPP-IV)) that cleaves a pair of N-terminal amino acids from the albumin, and (2) heating the albumin under conditions effective to cause the formation of the DKP. Further, treatment of DKP- and albumin- containing streams to produce improved, higher value, DKP compositions and purified albumin compositions for therapeutic uses is also disclosed. In addition to a first therapeutic DKP composition comprising a low albumin content, a second valuable therapeutic composition is also produced characterized by a high albumin concentration.
