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Reported herein is the sensitive and selective detection of bisphenol A (BPA) and six BPA derivatives in buffer and urine environments. This detection system relies on the ability of γ-cyclodextrin to act as a supramolecular scaffold to promote highly analyte-specific, proximity-induced fluorescence modulation of high quantum yield fluorophores, which led to unique modulation responses for each cyclodextrin–analyte–fluorophore combination investigated in both buffer and urine environments, and high selectivity between structurally similar analytes using linear discriminant analysis of the resulting response signals. This method was sensitive (low micromolar detection limits), selective (able to differentiate between structurally similar analytes), and broadly applicable (with successful detection in both buffer and urine environments), and has significant potential in the detection of BPA and its derivatives in a wide variety of complex environments.