Mastitis is one of the most costly diseases to the dairy cow industry. Implementation of management protocols have decreased the incidence rate of contagious mastitis pathogens, while the incidence of cases caused by environmental pathogens, such as Escherichia coli (E. coli) and Streptococcus uberis (Strep. uberis), remains unchanged. Currently, antibiotics are the primary therapy utilized to control mastitis. However, growing concern for antibiotic overuse, improper use and bacterial resistance have led to the examination of alternative strategies. Two promising alternative mitigation strategies were explored in the research leading to this dissertation. The first is a potent endolysin, PlyC, which has demonstrated bactericidal activity against several streptococcal species in a variety of applications. However, it is unknown how PlyC interacts with the bovine immune system. Varying doses of PlyC were non-toxic and did not alter the oxidative burst response of bovine neutrophils, the first immune cells recruited to the intramammary infection. The second alternative to an antimicrobial drug explored was citrus oil dissolved in ethanol. This was tested against E. coli strain P4. Prior antimicrobial investigations with citrus oil utilized dimethylsulfoxide as a carrier solvent, which is currently prohibited in the dairy industry. Citrus oil and its primary components were tested to determine minimum inhibitory, bactericidal and biofilm eradication concentrations. Citrus oil components, citral and linalool, demonstrated better antimicrobial activity than the native oil in vitro. In addition, citral and linalool were minimally toxic to bovine neutrophils and did not hinder their oxidative burst response in vitro. Because citral demonstrated greater antimicrobial activity than linalool, it was the logical candidate to test for the efficacy as an intramammary therapy against experimentally-induced E. coli mastitis. Unfortunately, citral treatment did not differ from a common intramammary antibiotic therapy or sterile buffered solution. In conclusion, the use of PlyC as an alternative therapy for Strep. uberis mastitis is promising as PlyC may not interfere with immune response during mastitis. The antimicrobial effects of citral may better serve as a disinfectant than a therapy for E. coli mastitis.