Of many drug candidates designed for treatment of type II diabetes, an exendin-4 (EX-4) analog from the substitutions of both beta-Asp for Glu3 and Tyrfor Glnl3 of EX-4 was found to have a prolongation in biological half life, an increase in cell proliferation and a remarkable improvement in reducing blood glucose with respect to EX-4. In this study, we applied CD and NMR approaches to characterize the structures of this active EX-4 analog in water, trifluoroethanol (TFE) aqueous solution, and dodecylphosphocholine (DPC) micelles and compared the results of the EX-4 analog with those of EX-4. Both EX-4 peptides adopt alpha-helix structures with the N-termini disordered and the C-terminal parts folded as hydrophobic clusters in these media. However, the analog has a longer helical extension in the N-terminal part than EX-4. The increasing helical turns may favor affinity for extracellular domain of glucagon-like peptide-1 receptor and accurate positioning of the crucial N-terminal residues in the transmembrane domains of the receptor. The analog has a stronger propensity to aggregate than the native EX-4, which is attributed to more coiled-coil interaction in the analog than in its native type. We also probed the association of EX-4 and its analog to DPC micelles and observed micelle-induced insertion of both peptides with their N- and C-termini as well as the central parts embedded in micelles and the residues near Asp9 and the residues around Trp25-Ser32 more water exposed. A single-step ligand-receptor binding model was suggested based on the analysis of these results.