Mercury contamination stemming from artisanal and small-scale gold mining (ASGM) operations poses significant environmental and health concerns. This study focuses on the Darmali area in River Nile State, Sudan, where the reprocessing of amalgamation tailings has led to mercury contamination. This study assessed the mercury content in soil and tailings samples, as well as in tap and groundwater, to evaluate the human health risks from ASGM activities and assess contamination levels within the study area. Soil and water samples were collected from various locations, including agricultural, residential, and tailings sites, as well as groundwater and tap water from the Nile. Mercury analysis was conducted using MA-3000 (NIC), and geo-accumulation index analysis revealed extreme pollution levels in areas with tailings and moderate pollution levels in agricultural and residential areas. Hazard quotients were applied to assess health risks, with inhalation of mercury vapor identified as the primary exposure route. The results indicated that tailings pose significant health risks, particularly for children, while water samples and soil from agricultural and residential areas did not pose significant risks. These findings underscore the urgent need for authorities and local communities to address mercury contamination by removing and treating tailings from affected areas to mitigate health risks.