Amending Pb-affected soil with biochar (BH) and magnesium potassium phosphate cement (MKC) reduces Pb uptake in plants. Moreover, foliar applications of melatonin and proline are also known to reduce plant oxidative stress and Pb uptake. However, little is known about combining both techniques, i.e., adding a combo immobilizing dose (CIA = mixture of BH and MKC at 50:50 ratio) in Pb-polluted soil and foliar application of proline and melatonin for reducing Pb uptake and oxidative stress in spinach. Control, proline, melatonin, CIA, CIA+proline, and CIA+melatonin were the treatments utilized in this pot study to see their effects on reducing plant oxidative stress, Pb uptake, and improving spinach quality in Pb-polluted soil. Moreover, Pb bioavailability, enzymatic activities, and numbers of bacteria, fungi, and actinomycetes in the soil were also evaluated. The effect of CIA on reducing Pb in the soil-plant system and improving soil enzymes and microbial numbers was more pronounced than melatonin alone. The most effective treatment was CIA+melatonin reducing Pb availability in soil (77%), shoots (95%), and roots (84%), alleviating oxidative stress, and improving plant biomass (98%) and nutrients. Soil enzymatic activities and the number of microorganisms in the rhizosphere were also highest with CIA+melatonin. Results highlight the significance of CIA+melatonin, as an inexpensive approach, in remediating Pb-polluted soil and improving spinach quality. However, further research is needed to understand the significance of CIA+melatonin on different crops and various soil Pb concentrations before employing this technique commercially in agriculture and environment sectors.