Abstract: In the uranium purification cycle of spent nuclear fuel reprocessing, a significant challenge is the unavoidably co-extraction of trace plutonium with uranium into the organic phase, which leads to unacceptable plutonium levels in the purified uranium product. To resolve this issue, two novel hydrophilic multiamide complexing agents—2,2'-(methylimino)bis(N,N-dimethylacetamide) (MIDMA) and N,N,N',N',N'',N''-hexamethyltriacetamide (NTAamideC1)—were designed and synthesized aimed at selectively back-extracting trace plutonium from a 30% TBP-kerosene organic phase. A comprehensive experimental study was conducted to evaluate the back-extraction performance of the two complexing agents. The effects of multiple variables were investigated, including contact time, nitric acid concentration (ranging from 0.5 mol/L to 5 mol/L), complexing agent concentration (0.01-0.1 mol/L), initial Pu(Ⅳ) concentration (10-500 μg/L), mass fraction of the degradation product dibutyl phosphate (DBP, 0.05%-1%), phase ratio (O/A from 1∶1 to 10∶1), and temperature (293-323 K). The results demonstrate that both complexing agents could achieve effective back-extraction of Pu(Ⅳ) under the conditions of low acidity, low plutonium concentration, and low DBP concentration. Remarkably, NTAamideC1 exhibits exceptional performance, maintaining a back-extraction efficiency above 99% even at nitric acid concentrations as high as 5 mol/L. Furthermore, it shows strong tolerance to high DBP content (80% back-extraction efficiency at 1% DBP) and performs well under high organic-to-aqueous phase ratios (90% back-extraction efficiency at O/A = 10∶1). In the presence of high concentration of uranium (76 g/L), NTAamideC1 selectively back-extracts Pu(Ⅳ) without significantly back-extracting U(Ⅵ), achieving a high separation factor (SF_U/Pu) of 609 at 1.5 mol/L HNO₃. This performance surpasses that of conventional complexing agents such as acetohydroxamic acid (AHA) and hydroxysemicarbazide (HSC). Thermodynamic analysis indicates that the back-extraction process is endothermic and entropy-driven, with negative Gibbs free energy values confirming spontaneity at room temperature. Density functional theory (DFT) calculations were employed to elucidate the coordination mechanism. The results reveal that NTAamideC1 forms a stable tetradentate complex with Pu(Ⅳ) via one central nitrogen atom and three carbonyl oxygen atoms. In contrast, its interaction with \mathrmUO_2^2+ is weaker. Detailed electronic structure analysis—including Mulliken charges, Mayer bond orders, molecular orbital energies, and electrostatic surfaces potential—provides further evidence for the stronger affinity and selectivity of NTAamideC1 toward Pu(Ⅳ) over U(Ⅵ). The smaller HOMO-LUMO gap and greater charge transfer in the Pu(Ⅳ) complex indicate stronger orbital interaction between Pu(Ⅳ) and NTAamideC1. These results show that the hydrophilic multiamide ligand NTAamideC1 demonstrates outstanding potential for the selective separation of trace plutonium from uranium in nuclear reprocessing process. Its high efficiency, excellent selectivity, and robustness under industrially relevant conditions make it a promising candidate for application in advanced nuclear fuel cycle processes, particularly in uranium purification cycles where high decontamination factors are required.