The general characteristics of ionophore antibiotics and the mechanisms of their antimicrobial action were analyzed. Two types of ionophore antibiotics are known: those that transport ions across the membrane, and those that form a channel in the cell membrane through which ions pass. Ionophore antibiotics used in animal husbandry belong to the former group (monensin, lasalocid, salinomycin, narasin). They are synthesized by bacteria of the Streptomyces genus. Bacterial cells and rumen fluid differ in ionic composition, which is regulated by active ion transport. As a result, the cytoplasm of bacteria contains more potassium ions, while the rumen fluid, on the contrary, has more sodium ions. Ionophores transport potassium inside the cell and remove sodium outside. The bacteria try to correct this imbalance and require ATP energy to carry out this process. Eventually, energy deficit develops in the bacterial cell and it dies. Ionophore antibiotics affect only the Gram-positive bacteria in the rumen of ruminants, because they cannot penetrate through the cell wall of Gram-negative bacteria. Thus, there is a selective destruction of some types of bacteria, the most sensitive among which are the so-called hyper-ammonia-producing bacteria (HAB). Ionophore antibiotics, which change the breakdown of protein and carbohydrates, change the ratio of volatile fatty acids by increasing the proportion of propionic acid and thus inhibit methanogenesis in the rumen. Ionophore antibiotics are an important antiketotic agent because they reduce the concentration of β-hydroxybutyrate and non-esterified fatty acids in the blood of ruminants. During the transition period, cows have metabolic disorders so they are more prone to infectious diseases due to a decrease in resistance. The use of ionophore antibiotics affects the immune function and resistance to inflammatory processes, which is caused by an indirect influence associated with a lower pathological effect of ketosis and steatosis. Ionophore antibiotics reduce the negative energy balance and its pathological impact on metabolism. The influence of ionophore antibiotics on cow’s milk productivity is mostly absent or insignificant. The study presents characteristics of biologically active substances of hop cones. Hop cones contain biologically active components similar to ionophore antibiotics by action. These are prenylated flavonoids: humulone (α-acid), lupulone (β-acid) and their derivatives. These components of hop cones can be regarded as a potential substitute for ionophoric antibiotics. In particular, lupulone and some other components of hop cones inhibit the activity of Gram-positive bacteria, causing reactions similar to ionophore antibiotics. In addition, hop cones have many other biologically active compounds: phenols, essential oils, and resins, which have antimicrobial, antioxidant, sedative, phytoestrogen, insulin stimulating, immunomodulatory, and antitumor effects.