This study investigates the extent and spatial distribution of Potentially Toxic Elements (PTEs) in the Djebel Onk phosphate mine area in south-eastern Algeria, as well as the associated risks to human health. Various scales are considered and sampled, including tailing waste (n = 8), surrounding farmland soil (n = 21), and sediments (n = 5). The samples were mineralogically and chemically analyzed using XRD, FTIR, XRF, and ICP-MS techniques. Principal Component Analysis (PCA) was applied after transforming the raw data into centered-log ratios (clr) to identify the dominant factors controlling the distribution of PTEs. Furthermore, pollution assessment was conducted using several indices, including geo-accumulation, pollution load, contamination security indices, and enrichment and contamination factors. The results reveal that the analyzed samples are mostly P-enriched in the mine tailings, farmland soil, and sediments, with P2O5 concentrations ranging from 13.37 wt% to 26.17 wt%, 0.91–21.70 wt%, and 17.04–29.41 wt%, respectively. The spatial distribution of PTEs exhibits clearly a decrease in the contents of CaO, P2O5, Cr, Sr, Cd, and U with increasing distance from the mine discharge site, while other oxides, such as MgO, Al2O3, SiO2, K2O, and Fe2O3, and associated elements (Cu, Co, Pb, and Zn), show an increase. PCA confirms the influence of minerals such as, apatite, dolomite, and silicates on the distribution PTEs. It denoted that the highest contamination level of all PTEs in soils and sediments was observed in the southern part of the plant and mine tailings compared to the northern part. In terms of human health risks, the assessment reveals that the hazard index (HI) values for both non-carcinogenic and carcinogenic risks associated with PTEs in the study area are below 1, suggesting no significant risk. However, regardless of the sample type, the lifetime cancer risk (LCR) values vary from 1.69E-05–2.11E-03 and from 1.03E-04–2.27E-04 for Cr, Ni, As (children) and Cd (adults), respectively, exceeding the safe levels recommended by the United States Environmental Protection Agency. The study highlights that oral ingestion poses the greatest risk, followed by dermal contact and particle inhalation. Importantly, all these indices decrease with increasing distance from the sampling site to the waste discharge point and the factory, which indicates that the phosphate mining activity had caused some extent risks. These findings provide valuable insights for mitigating the adverse health impacts and guiding environmental management efforts.