Crop manganese (Mn) accumulation and the associated human health risks stemming from excessive intake of high Mn crop foods have attracted attention. However, there is limited information available concerning the impact of plastic film mulching (PFM) on Mn concentration in cereal grains and the health risks associated with Mn intake by the human body. Field experiments were conducted from 2014 to 2016 at seven sites in the drylands of a typical wheat-growing region in China to assess the effect of PFM on grain Mn concentration, Mn accumulation and distribution in winter wheat plants, and the potential risk of Mn intake and optimal grain intake for human health. The multi-site study results revealed that grain Mn concentration and bioavailability were significantly higher under PFM compared to no mulching. Similarly, PFM was found to enhance aboveground Mn accumulation at the anthesis stage by 17.5 %, Mn harvest index by 3.9 %, grain Mn accumulation by 28.9 %, and available Mn concentration in the soil by 10.9 %. The increased uptake and accumulation of Mn in wheat plants, leading to elevated grain Mn concentration, were primarily attributed to the improved availability of Mn and moisture in the soil under PFM treatment. Furthermore, a health risk assessment indicated that long-term consumption of whole wheat grains from PFM treatment could potentially pose a non-carcinogenic risk of Mn for children and adolescents residing in rural areas. Therefore, this study established upper limits for daily consumption of whole wheat grains based on the specific needs of local residents. The findings of this research underscore the potential health risks associated with consuming grain crops grown in PFM crop production systems.