Display omitted •Root tuber had accumulated U and Cd, and would pose a health risk if consumed.•Both U and Cd significantly interfered with the mineral nutrient of the roots.•A total of 4865 root metabolites were identified using UPLC-MS analysis.•U and Cd induced the expression of plant hormones and cyclic nucleotides.•U and Cd had significant inhibitory effects on the pyrimidine metabolic pathway. The purpose of this study was to reveal the absorption and interaction mechanisms of uranium (U) & cadmium (Cd) in corps. Purple sweet potato (Ipomoea batatas L.) was selected as the experimental material. The absorption behavior of U and Cd in this crop and the effects on mineral nutrition were analyzed in a pot experiment. The interactions between U and Cd in purple sweet potato were analyzed using UPLC-MS metabolome analysis. The pot experiment confirmed that the root tuber of the purple sweet potato had accumulated U (1.68–5.16 mg kg−1) and Cd (0.78–2.02 mg kg−1) and would pose a health risk if consumed. Both U and Cd significantly interfered with the mineral nutrient of the roots. Metabolomics revealed that a total of 4865 metabolites were identified in roots. 643 (419 up; 224 down), 526 (332 up; 194 down) and 634 (428 up; 214 down) different metabolites (DEMs) were identified in the U, Cd, and U + Cd exposure groups. Metabolic pathway analysis showed that U and Cd induced the expression of plant hormones (the first messengers) and cyclic nucleotides (cAMP and cGMP, second messengers) in cells and regulated the primary/secondary metabolism of roots to induce resistance to U and Cd toxicity.