Purpose <p>Cadmium contamination in agricultural soils poses significant risks to food safety and ecosystem health. This study investigated the synergistic effects of humic substances (fulvic acid [FA] or humic acid [HA]) and nitrogen (N) fertilisers on enhancing cadmium (Cd) phytoextraction by <i>Solanum nigrum</i> L. (<i>S. nigrum</i><b>)</b> in moderately contaminated soils.</p> Methods <p>A pot experiment tested ten treatments combining FA/HA with ammonium sulphate ((NH₄)₂SO₄), urea (CH₄N₂O), ammonium chloride (NH₄Cl), or ammonium bicarbonate (NH₄HCO₃), measuring plant biomass, Cd uptake, physiological responses, the expression levels of three antioxidant enzyme genes and soil parameters.</p> Results <p>Co-application of FA with (NH₄)₂SO₄ yielded the highest shoot biomass and Cd extraction relative to the control. Biomass augmentation drove these improvements, as Cd concentrations in shoots remained statistically unchanged across treatments. Physiological analysis revealed reduced oxidative stress (H₂O₂ and MDA levels), elevated antioxidant enzyme activities (SOD and POD) in shoots under combined treatments, meanwhile, the relative expression levels of <i>SnCAT</i>, <i>SnPOD</i> and <i>SnSOD</i> were clearly changed. Soil pH and bioavailable Cd concentrations remained stable, minimising risks of Cd leaching or mobilisation. The results demonstrate that FA or HA combined with ammonium-based fertilisers significantly accelerates Cd phytoextraction by circumventing the “dilution through growth” effect observed in other species, maintaining high Cd uptake efficiency.</p> Conclusions <p>The FA + (NH₄)₂SO₄ treatment emerged as the optimal strategy, offering a practical solution for remediating moderately Cd-contaminated soils within a decade. These findings provide a scalable framework for integrating <i>S. nigrum</i>-based phytoremediation into agricultural systems, particularly where soil buffering capacity limits amendment-induced pH fluctuations.</p>