Suspended particulate matter (SPM) is one of the dominant water constituents in inland and coastal waters, and SPM concnetration (CSPM) is a key parameter describing water quality. This study, using in-situ spectral and CSPM measurements as well as Sentinel 2 Multispectral Imager (MSI) images, aimed to develop CSPM retrieval models and further to estimate the CSPM values of Poyang Lake, China. Sixty-eight in-situ hyperspectral measurements and relative spectral response function were applied to simulate Sentinel 2 MIS spectra. Thirty-four samples were used to calibrate and the left samples were used to validate CSPM retrieval models, respectively. The developed models were then applied to two Sentinel 2 MSI images captured in wet and dry seasons, and the derived CSPM values were compared with those derived from MODIS B1 (λ = 645 nm). Results showed that the Sentinel 2 MSI B4–B8b models achieved acceptable to high fitting accuracies, which explained 81–93% of the variation of CSPM. The validation results also showed the reliability of these six models, and the estimated CSPM explained 77–93% of the variation of measured CSPM with the mean absolute percentage error (MAPE) ranging from 36.87% to 21.54%. Among those, a model based on B7 (λ = 783 nm) appeared to be the most accurate one. The Sentinel 2 MSI-derived CSPM values were generally consistent in spatial distribution and magnitude with those derived from MODIS. The CSPM derived from Sentinel 2 MSI B7 showed the highest consistency with MODIS on 15 August 2016, while the Sentinel 2 MSI B4 (λ = 665 nm) produced the highest consistency with MODIS on 2 April 2017. Overall, this study demonstrated the applicability of Sentinel 2 MSI for CSPM retrieval in Poyang Lake, and the Sentinel 2 MSI B4 and B7 are recommended for low and high loadings of SPM, respectively.