The Normalized Difference Vegetation Index (NDVI) is a crucial remote-sensing metric for assessing land surface vegetation greenness, essential for various studies encompassing phenology, ecology, hydrology, etc. However, effective applications of NDVI data are hindered by data noise due to factors such as cloud contamination, posing challenges for accurate observation. In this study, we proposed a novel approach for employing a Temporal-Difference Graph (TDG) method to reconstruct low-quality pixels in NDVI data. Regarding spatio-temporal NDVI data as a time-varying graph signal, the developed method utilized an optimization algorithm to maximize the spatial smoothness of temporal differences while preserving the spatial NDVI pattern. This approach was further evaluated by reconstructing MODIS/Terra Vegetation Indices 16-Day L3 Global 250 m Grid (MOD13Q1) products over Northwest China. Through quantitative comparison with a previous state-of-the-art method, the Savitzky–Golay (SG) filter method, the obtained results demonstrated the superior performance of the TDG method, and highly accurate results were achieved in both the temporal and spatial domains irrespective of noise types (positively-biased, negatively-biased, or linearly-interpolated noise). In addition, the TDG-based optimization approach shows great robustness to noise intensity within spatio-temporal NDVI data, suggesting promising prospects for its application to similar datasets.