DNA aptamer conjugated single-walled carbon nanotube (Aptamer-SWNT) hybrids have demonstrated effective optical biosensors because of their high selectivity and specificity to a target protein, however, the understanding of SWNT hybridization with an aptamer forming a secondary or tertiary structure is still lacking. We study wrapping methods dependent optical biosensing modulation by insulin and platelet-derived growth factor (PDGF) using the Aptamer-SWNT hybrids and the Aptamer-Anchor-SWNT hybrids with a periodically sequenced single-stranded DNA (ssDNA) as anchoring phases. We observe that the refolding nature of the aptamer and its combination with an anchoring phase are critical to the hybridization, where the remarkable optical sensing properties are attributed to the wrapping procedures including the direct wrapping with sonication and the indirect wrapping through dialysis. The tetrameric parallel-stranded G-quadrupole conformation of insulin binding aptamers (IBA) shows an enhanced fluorescence response quenching when using the directly wrapped Aptamer-Anchor-SWNT hybrids. In addition, helix-structural refolding of PDGF binding aptamers (PBA) indirectly wrapped on the SWNT vicinity is influenced by anchoring length for optical modulation. Furthermore, the consecutive centrifuging processes with the indirect wrapping demonstrate fluorescence response brightening, in which the diameter dependent brightening effect is observed by aptamer-protein interactions. This study provides an understanding the underlying conjugation nature of both the Aptamer-SWNT and the Aptamer-Anchor-SWNT hybrids formation, facilitating exceptional optical sensing modules with consideration of refolding feature of aptamers, selection of anchoring phases, wrapping methods and centrifuging process, and the hybridization voyage for DNA-SWNT platforms maneuvers their outcoming optical biosensing capabilities.