A series of novel bis-indole compounds, 1,omega-bis(((3-acetamino-5-methoxy-2-methylindole)-2-methylene)phenoxy)alkane, have been designed and synthesized on the basis of the enzyme structure of human nonpancreatic secretory phospholipase A2 (hnps PLA2). Their inhibition activities against hnps PLA2 were improved compared to that of the monofunctional protocompound. These bivalent ligands not only inhibited hnps PLA2 but also drove the dimerization of hnps PLA2. Their dimerization ability correlated with the linker length and position. Further study on the potent compound 5 (1,5-bis(((3-acetamino-5-methoxy-2-methylindole)-2-methylene)phenoxy)pentane, IC50 = 24 nM) revealed that cooperative binding interactions between the two enzyme molecules also contributed to the stability of the ternary complex. The combination of bivalent ligands and hnps PLA2 can be used as a novel chemically induced dimerization (CID) system for designing regulatory inhibitors.