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Herein, a facile and sensitive dual mode sensing strategy for amantadine (AMD) level evaluation by coupling the plasmonic Au nanorod (NR) and supramolecular SH-cyclodextrin (CD) through strong Au-S bond is proposed. Methylene blue (MB) molecules can be inserted into the cavity of CD molecules through the hydrophobic interaction, which would cause the plasmon resonance energy transfer (PRET) process as well as electrochemical signal response due to the spectrum overlap between Au NR and MB molecules and the electrochemical conversion activity of MB molecules. Subsequently, AMD would induce the replacement of MB molecules because of the stronger interaction with CD, resulting the recovery of scattering intensity of Au NR and decrease of the electrooxidation current of MB. On one hand, the increase of Au NR scattering intensity is linearly proportional to AMD with the concentration from 0.4 to 3.0 μM, and reaches a limit of detection (LOD) of 0.28 μM. On the other hand, electrochemical measurement method enlarged the detection range of AMD. The variation of electrochemical oxidation peak current of MB is linearly proportional to the logarithm value of AMD concentration from 2.5 to 375.0 μM, with LOD of 1.9 μM. Subsequently, the proposed dual mode response sensing strategy was successfully employed for the detection of AMD in human serum samples with great selectivity and sensitivity, with a recovery percentage ranged from 92.6 to 112.0%. Overall, this Au NR@SH-CD-MB nanoparticle based single particle plasmonic and electrochemical dual mode sensing method provides great potential in the field of clinical drug detection or metabolic process investigation in the future. Au NR@SH-CD-MB NPs for dual mode AMD detection. [Display omitted] • The CD molecules were introduced for simpler and more effective construction of PRET based plasmonic sensors. • Au NR@SH-CD-MB NPs could produce scattering and electrochemical dual signals for AMD detection. • The prepared Au NR@SH-CD-MB NPs have a good sensitivity and selectivity toward AMD. • The dual signal responsive detection method could achieve a lower LOD and broader dynamic range in biosensing. [ABSTRACT FROM AUTHOR]