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To date, various G-quadruplex structures have been reported in human telomeric sequences. Human telomeric repeats can form many topological structures depending on conditions and on base modification; parallel, antiparallel, and hybrid forms. The effect of salts and some specific ligands on conformational switches between different conformers is known, but the influence of protruding sequences has rarely been discussed. In this paper, we analyze different quadruplex-forming oligomers derived from human telomeric sequences which contain 3′- and 5′-protruding nucleotides, not usually associated with the G-quadruplex motif. The study was performed using electrophoresis, CD, and UV spectroscopies. The major findings are (i) protruding nucleotides destabilize the G-quadruplex structure, and (ii) overhanging sequences influence the folding of the quadruplex.