A sensitive and selective fluorescence quenching method was developed for the determination of lurasidone using MPA-CdTe quantum dots as a "turn-off" fluorescent probe. The fluorescence intensity of the MPA-CdTe QDs was quenched upon the addition of lurasidone, with the quenching efficiency exhibiting a linear relationship with the lurasidone concentration in the range of 0.02-1.0 μg mL. Stern-Volmer analysis revealed that the quenching mechanism was predominantly static in nature, and thermodynamic studies indicated that the interaction between lurasidone and MPA-CdTe QDs was exothermic and spontaneous in nature. Factors affecting the quenching process, including pH, MPA-CdTe QDs volume, and incubation time, were optimized using a Box-Behnken experimental design. A significant model was obtained with a coefficient of determination ( ) of 0.9547, demonstrating the reliability of the optimization process. The analytical performance of the method was validated according to ICH guidelines, exhibiting good linearity and sensitivity with LOD of 5.90 ng mL and LOQ of 17.70 ng mL. The accuracy and precision of the method were assessed through recovery studies, showing satisfactory results with a mean recovery of 98.65 ± 0.733% and RSD% > 2%. The proposed method was successfully applied to the analysis of lurasidone in pharmaceutical dosage forms, spiked plasma, and environmental water samples, with good recoveries and precision. The greenness and analytical practicality of the method were evaluated using AGREE and BAGI tools, respectively, and the results showed that the proposed method is a greener and more practical alternative to previously reported analytical techniques for the determination of lurasidone. The present study demonstrates the potential of MPA-CdTe QDs as a sensitive and selective fluorescent probe for the determination of lurasidone in various matrices, with good analytical performance and environmental compatibility.