Although PEGylation is widely used in biomedicine with great success, it suffers from many drawbacks, such as polydispersity, nonbiodegradability, and loss of precursor potency. Recently, the search for polyethylene glycol (PEG) substitutes has attracted considerable attention. Some of the substitutes partially address the drawbacks of PEGs, but sacrifice the “stealth” effect of PEGs and bring in new issues. Herein, we developed monodisperse oligoethylene glycol (M-OEG) polyamides over 5000 Da as biodegradable and monodisperse PEGylation (M-PEGylation) agents, which provided M-PEGylated peptides and proteins with high monodispersity and a biodegradable PEG moiety. Compared to regular PEGylated proteins with a complex “stealth” cloud of PEG, the hydrogen bond interactions between the M-OEG polyamides and proteins provided the M-PEGylated protein with a biodegradable “stealth” cloak. The monodisperse and biodegradable M-PEGylation strategy as well as the peculiar protein–M-OEG polyamide interactions may shed light on many long-lasting issues during the development of PEGylated biologic drugs, such as monodispersity, biodegradability, and tunable conformation.