Pharmaceuticals and personal care products (PPCPs) are emerging contaminants widely detected in natural environments, primarily in freshwater sources and wastewater. Currently, an extensive database of cases of detection of PPCPs in soils has been collected, and the problem of pollution with these emerging substances is especially relevant for agricultural landscapes. The study aimed to assess the influence of selected PPCPs on the processes occurring in the soils, especially in the rhizosphere, on the example of a test plant. As a working hypothesis, it was suggested that the introduction of selected PPCPs could change the biochemical processes in the rhizosphere, affecting the activity of the microbial community and, therefore, the characteristics of the labile pool of soil organic matter represented by watersoluble forms could change. In a short-term incubation experiment on the humus horizon of chernozem soil, we studied the effect of PPCPs represented by the most frequently prescribed therapeutic groups and often found in natural environments: ciprofloxacin (antibiotic), ketoprofen (analgesic), atenolol (beta-blocker), clotrimazole (antifungal agent). Selected substances were applied to the soil in concentration gradients. Lettuce (Lactúca sativa L.) was used as a test plant. At the end of the experiment, the biomass of shoots and roots and urease enzymatic activity in variants treated by PPCPs differed significantly from the control. Mainly, differences from control samples were expressed in the inhibitory effect; at the same time, an increase in indicators values was observed in several cases. A change in the composition of dissolved organic matter in the rhizosphere soil was noted: in general, even in low concentrations, samples treated with ciprofloxacin, ketoprofen, and atenolol differed from the control variant. While the changes were irregular in terms of concentrations of PPCPs, the observed effects caused by the introduction of selected substances can be explained by both the studied soil’s buffer capacity and the soil’s biological activity, particularly the rhizosphere community.