Tryptophan (Trp) is very necessary for biosystems; therefore, high-efficient detection of Trp is an important subject. Hereof, based on our early research works on fluorescent sensors, we rationally designed and synthesized a fluorescent sensor (SNP5) based on N-(2-aminoethyl)-2-(hexylthio) acetamide-functionalized pillar[5]arene, which showed high selectivity and sensitive recognition for L-Trp (LOD = 2.19 x 10(-8 )M). Moreover, SNP5 exhibited aggregation-induced emission enhancement fluorescence. Within SNP5, the pillar[5]arene group could act as N-H center dot center dot center dot pi- and C-H center dot center dot center dot pi-interaction sites, as well as a H-bond-interaction site; meanwhile, the N-(2-aminoethyl)-2-(hexylthio) acetamide group also served as a multihydrogen-bonding site. As a result, SNP5 could selectively detect L-Trp through the synergy of the pillar[5]arene group and the N-(2-aminoethyl)-2-(hexylthio) acetamide group. Compared with previous work, the results of this work support the strategy that changing the functionalized group of the pillar[5]arene can adjust the selectivity of the pillar[5]arene-based sensor and achieve the detection of different amino acids. The detection mechanism was specifically researched through experiments and theoretical calculations including frontier orbitals, electrostatic potential, and the independent gradient model approach. Interestingly, these theoretical calculations not only supported the experimental results but also provided a visualized understanding of guest-adaptive multisupramolecular interactions between SNP5 and L-Trp.