Synthetic peptides with defined secondary structure scaffolds, namely hairpins and helices, containing tryptophan residues, have been investigated in this study to probe the influence of a large number of aromatic amino acids on backbone conformations. Solution NMR investigations of $Boc-W-L-W-^DP-G-W-L-W-OMe$ (peptide 1), designed to form a well-folded hairpin, clearly indicates the influence of flanking aromatic residues at the DPro–Gly region on both turn nucleation and strand propagation. Indole–pyrrolidine interactions in this peptide lead to the formation of the less-frequent type $I'$ turn at the $^DPro–Gly$ segment and frayed strand regions, with the strand residues adopting local helical conformations. An analog of peptide 1 with an Aib–Gly turn-nucleated hairpin (Boc-W-L-WU- G-W-L-W-OMe (peptide 2)) shows a preference for helical structures in solution, in both chloroform and methanol. Peptides with either one (Boc-W-L-W-U-W-LW- OMe (peptide 3)) or two (Boc-U-W-L-W-U-W-L-WOMe (peptide 4)) helix-nucleating Aib residues give rise to the well-folded helical conformations in the chloroform solution. The results are indicative of a preference for helical folding in peptides containing a large number of Trp residues. Investigation of a tetrapeptide analog of peptide 2, Boc-W-U-G-W-OMe (peptide 5), in solution and in the crystal state (by X-ray diffraction), also indicates a preference for a helical fold. Additionally, peptide 5 is stabilized in crystals by both aromatic interactions and an array of weak interactions. Examination of Trp-rich sequences in protein structures, however, reveals no secondary structure preference, suggesting that other stabilizing interactions in a well-folded protein may offset the influence of indole rings on backbone conformations.