A series of novel l-lysine derivatives were designed, synthesized, and assayed for their inhibitory activities on amino-peptidase N (APN)/CD13 and matrix metalloproteinase-2 (MMP-2). The preliminary biological test showed that most of the compounds displayed a high inhibitory activity against MMP-2 and a low activity against APN except compound B6 which exhibited good potency (IC 50 = 13.2 μM) similar with APN inhibitor Bestatin (IC 50=15.5 μM), and could be used as lead compound in the future.