To compare multiplexed sensitivity-encoding diffusion-weighted magnetic resonance imaging (MUSE-DWI) and conventional DWI (cDWI) techniques in thyroid MRI. Nineteen patients who underwent thyroid MRI using both MUSE-DWI and cDWI at a 3.0T MRI system were enrolled. Qualitative parameters (image quality, thyroid contour, and lesion conspicuity) and quantitative parameters (signal-to-noise ratio (SNR), lesion-to-thyroid contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC)) were compared between the two sequences. In addition, ADC values derived from MUSE-DWI and cDWI were separately compared between benign and malignant lesions. MUSE-DWI outperformed cDWI in terms of image quality, thyroid contour, and lesion conspicuity. Significantly, higher signal-to-noise ratio (SNR) in both the thyroid and its lesion were found in MUSE-DWI than those in cDWI (both P < 0.05). The lesion-to-thyroid contrast-to-noise ratio (CNR) values were also significantly higher in MUSE-DWI than those in cDWI (P < 0.05). The apparent diffusion coefficient (ADC) of the thyroid in MUSE-DWI was significantly lower than that in cDWI (P < 0.05). The ADC of the lesion in MUSE-DWI was also significantly lower than that in cDWI (P < 0.05). In addition, ADC values derived from MUSE-DWI and cDWI were significantly higher in benign lesions than malignant lesions (P < 0.05). Compared with cDWI, MUSE-DWI can improve the image quality, thyroid contour sharpness, lesion conspicuity, SNR in both the thyroid and its lesions, and enhancing the CNR between lesions and thyroid.