As our ongoing work, a series of peptidomimetic L-iso-glutamine derivatives derived from antineoplaston AS2-5 scaffold were prepared and their APN/CD13 and MMP-2 inhibitory activities were evaluated hereby. The results displayed that these compounds exhibited selective inhibition against APN as compared with MMP-2, with IC(50) values in micromole range. Compounds A1 and A2 showed comparable APN inhibitory activities than the positive control bestatin.