The purpose of this research is to develop and test a new approach to prevent clostridial disease in cattle, based on the use of a new compound biologically active feed additive (BFA). Some properties of the separate components of BFA are characterized. The research showed that a strain of the bacterium Bacillus amyloliquefaciens159 has an expressed antagonism to toxin-producing strains of C. perfringens. When using the test strains of C. perfringens from the ATCC collection (13124 as type A, 10543 as type C, 12916 as type F), the anticlostridial activity of the tested strains varied, with size range of 14.0 ± 0.95–15.0 ± 1.28 mm of delayed growth zones. The bactericidal properties of lauric acid and the sorption properties of diatomaceous earth, included in BFA, were confirmed. The experiment was conducted on Holstein cows at the beginning of lactation (control, C (n = 15) vs. experimental E48 (n = 15), E80 (n = 15) and E112 (n = 15), 48, 80 and 112 g/head/day BFA, respectively. All cows were vaccinated with “Coglavax” (vaccine against bovine and sheep clostridial disease, Ceva-Phylaxia VeterinaryBiologicals, Hungary), reinjected two weeks before the experiment. At the end of the experiment (3.5 months after the vaccination and 3 months after the start of BFA feeding according to the scheme of the experiment), the immune response in the control and Group E48 to C. perfringens β-toxin remained at the initial level, while the response in Group E80 and Group E112 became higher under the influence of BFA feeding. Cows fed BFA saw a guaranteed improvement in non-specific resistance. The increase in serum lysozyme concentration in cows of Groups E was 1.01–2.91 mkg/mL vs. control (p < 0.001). TP, GLB, ALB/GLB vs. Groups C and E48 (p < 0.001); this stabilized and normalized while feeding Group E80 and E112 animals with BFA. They also had improved nitrogen, fat, mineral metabolism, as indicated by significant increase in ALB (p < 0.05), UREA (p < 0.01), CHOL (p < 0.01), and CHL (p < 0.01) vs. Groups C and E48. Consumption of BFA increased the amount of anti-oxidants in the blood (highest TAWSA values in Group E80 14.45 mg/g, p = 0.002). Serum TBA–AP/ CP ratio was directly related to TBA–AP (r = 0.87, p < 0.001), and decreased in Group E80. The milk productivity increased under the action of BFA; the average daily milk yield of the cows from the experimental groups for the period of the experiment (d0-d98) was 1.24–1.66 kg higher than that of the control. At the same time, Group E112 cows had a significant increase in milk yield (by 5.1%, p = 0.03 vs. Control). Thus, feeding BFA to dairy cows was found to improve resistance, prevent toxicoses and increase milk production of cattle, which can serve as an additional strategy for bioprotection of cattle against infection.