Background and study objectives: The low soil quality status and the high concentrations of potentially toxic elements (PTEs) found in gold mine tailings make them unfit for crop production. Assessing the possibility of mine tailings for crop production after mining is important since the presence of these PTEs harms food safety and human health. In this study, we aimed to investigate the effects of biochar, poultry litter compost, and inorganic fertilizer on the uptake of PTEs and the soil quality improvement of tailings from a decommissioned mine tailing in Ghana.Materials and methods: Rice husk biochar, poultry litter compost, and NPK were applied alone or in combination to the abandoned mine tailings at the rate of 5 t ha−1. After a 42-day pot experiment, we extracted the content of nutrients and PTEs in the soil and plant, and determined their uptake by the Lactuca sativa L.Results and discussion: Rice husk biochar, poultry litter compost and NPK applied alone or in combination significantly increased the soil pH, organic matter, available P as well as the CEC (Ca2+, K+, Mg2+, Na+) but reduced the exchangeable acidity in the mine tailings. Additionally, tailings amended with NPK increased the N uptake by 42%. Also, tailings amended with 2.5 t ha−1 biochar + 2.5 t ha−1 NPK increased both P and K uptake by 128% and 101%, respectively. For PTE uptake (i.e., Pb, Hg, As, Cd, and Cr), biochar, poultry litter compost and their combinations reduced the Hg uptake (mg kg−1) in the pot by a maximum 49% as compared to the control. Plausible formation of metal-hydroxo complexes at high pH with its consequent strong adsorption of Hg and presence of exchangeable K which contributed to the ion binding strength of the amended mine tailings reduced mobility and uptake of Hg by the lettuce. However, biochar, compost, and/or inorganic fertilizer enhanced Cd, Cr, and Pb uptake, which may pose lettuce food chain contamination problems for the inhabitants.Conclusion: As a result, we conclude that the use of inorganic NPK fertilizer and rice husk biochar can be used to improve the soil quality of abandoned gold mine tailings for safe food production, minimize Hg uptake by lettuce, and lower the associated environmental risk.