Plant extracts are now being used to improve animals’ hematological activity, biochemistry, and immunology. This study aimed to assess the antimicrobial activity of Ziziphus nummularia against E. coli bacteria, which causes bovine mastitis in cattle. In this study, the experimental animals were divided into four groups. The control group (Group 0) was fed a normal diet throughout the experiment. In contrast, Groups 1, 2, and 3 received 100 g, 200 g, and 300 g of Ziziphus nummularia with their normal diet, respectively. At the end of the experiment, hematological parameters showed significant differences in the experimental groups. Biochemical parameters had significant differences in creatinine, ALT, and bilirubin; however, albumin values were moderately significant. The antimicrobial activity of Ziziphus nummularia extract was also assessed at different dilutions (0.6 ml, 0.8 ml, and 1 ml), with the 1 ml dilution showing a larger zone of inhibition compared to the others. Analysis of somatic cell count in milk revealed that Groups 2 and 3 showed a significant decrease compared to the control and Group 1. Therefore, incorporating Ziziphus nummularia into the regular diet of dairy animals is recommended to boost immunity against diseases like bovine mastitis, enabling farmers to manage mastitis effectively and enhance milk production in dairy cattle.