α-MMC and MAP30 as potential therapeutic proteins possess biological activities such as inhibiting protein biosynthesis (ribosome inactivation), 11 antitumor, antivirus, and, especially, anti-HIV replication. 7, 12, 13 However, as foreign proteins are like other potential therapeutic proteins, poor biocompatibility limits their further development and application. To overcome these problems, in this study we first purified the two main proteins from bitter melon seeds and carried out their PEGylation using a branched 20 kDa (mPEG) 2 -Lys-NHS directed specifically to lysil ε-amino groups. Homogeneous one-mer, two-mer, and three-mer PEG-RIPs were then identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). Not only was their immunogenicity in vivo remarkably decreased but also, importantly, their antitumor and antivirus activities in vitro were moderately influenced when compared with the un-PEGylated counterparts. This work is just the beginning step towards them being used clinically. The application of PEGylation and nanotechnolgy may indicate that the potential application of both α-MMC and MAP30 can be developed for antitumor and antivirus agents in the future.