The application of natural fertilizer mixtures that improve nutrient retention ability of soils has attracted considerable attention in recent years. In addition to rock phosphate (RP), the basic components of these mixtures are zeolites modified with selected cations, such as the ammonium ion. The NH4-zeolite serves as a carrier of nutrients as well as a soil conditioner, and it promotes the RP dissolution in all soil types. The purpose of the present work was to prepare cost-effective NH4-zeolite supplement, using 32 full factorial experimental designs, with concentration of modifier and processing time as variables. Saturation processes were carried out on two types of natural zeolites, K- clinoptilolite (K-Cp) and Ca-clinoptilolite (Ca-Cp). The Response Surface Method (RSM) was applied for evaluation of cation exchange, suggesting an effective modification of natural zeolite at lower quantities of modifier than commonly found in other studies on the topic. Using Principal Component Analysis (PCA), differences between samples relative to the process variables were clearly outlined and correlated with concentrations of the exchanged cations. The best results were obtained for the K-Cp type modified with 1.5 m solution of ammonium sulfate (at a stochiometric ratio 1:7.5) for all three processing intervals. By optimizing the modification process parameters, an experimental design of partially saturated NH4-Cp supplement that has the potential to supply all major plant nutrients was proposed.