Anionic boron clusters are man-made, inorganic compounds with potential applications in therapeutic peptides modification to improve their biological activity and pharmacokinetics, e.g., by enabling complexation with serum albumin. However, the conjugation of anionic boron clusters and peptides remains poorly understood. Here, we report a solid-state, thermal reaction to selectively conjugate carboxylic groups in the peptide thymosin β4 (Tβ4) with cyclic oxonium derivatives of anionic boron clusters (dodecaborate anion [B12H12]2- and cobalt bis(1,2-dicarbollide), [COSAN]- [3,3'-Co(1,2-C2B9H11)2]-). Modification of the carboxylic groups retains the negative charge at the modification site and leads to the formation of ester bonds. The ester bonds in the conjugates undergo hydrolysis at different rates depending on the site of the modification. We obtained conjugates with dramatically different stabilities (τ1/2 from 3-836 h (Tβ4-[B12H12]2- conjugates) and 9-1329 h (Tβ4-[COSAN]- conjugates)) while retaining or improving the prosurvival activity of Tβ4 toward cardiomyocytes (H9C2 cell line).