In this age of intensive industrialization and urbanization, mankind’s highest concern should be to analyze the effect of all metals accumulating in the environment, both those considered toxic and trace elements. With this aim in mind, a unique study was conducted to determine the potentially negative impact of Sn2+, Co2+, and Mo5+ in optimal and increased doses on soil biological properties. These metals were applied in the form of aqueous solutions of Sn2+ (SnCl2.2H2O), Co2+ (CoCl2 · 6H2O), and Mo5+ (MoCl5), each in the doses of 0, 25, 50, 100, 200, 400, and 800 mg kg−1 soil DM. The activity of dehydrogenases, urease, acid phosphatase, alkaline phosphatase, arylsulfatase, and catalase and the counts of twelve microorganism groups were determined on the 25th and 50th day of experiment duration. Moreover, to present the studied problem comprehensively, changes in the biochemical activity and yield of spring barley were shown using soil and plant resistance indices—RS. The study shows that Sn2+, Co2+, and Mo5+ disturb the state of soil homeostasis. Co2+ and Mo5+ proved the greatest soil biological activity inhibitors. The residence of these metals in soil, particularly Co2+, also generated a drastic decrease in the value of spring barley resistance. Only Sn2+ did not disrupt its yielding. The studied enzymes can be arranged as follows for their sensitivity to Sn2+, Co2+, Mo5+: Deh > Ure > Aryl > Pal > Pac > Cat. Dehydrogenases and urease may be reliable soil health indicators.