Mastitis remains one of the most significant diseases in dairy cattle, leading to reduced milk yield and quality, increased treatment costs, premature culling, and shortened herd longevity, thereby imposing considerable economic losses on the dairy industry. Conventional antibiotic-based therapies, despite their relative efficacy, are associated with major challenges such as drug costs, antibiotic residues in milk, extended withdrawal periods, and, most critically, the emergence of antimicrobial resistance (AMR). This issue not only threatens animal health but also raises serious concerns for food safety and public health. In recent years, non-antibiotic alternatives such as phage therapy, bacteriocins, probiotics, postbiotics, nanotechnology-based formulations, and novel compounds like pectin have been introduced as promising candidates. Most of these findings have been generated in laboratory settings or small animal models; however, their translation to live animals and field conditions continues to face multiple barriers. Intramammary formulations represent a critical turning point in this process, playing a fundamental role in efficacy, stability, controlled release, and tissue safety of these agents. Current evidence indicates that many non-antibiotic compounds perform effectively in vitro but are influenced by pharmacological and physiological constraints within the living udder. Moreover, robust data on their capacity to reduce antibiotic consumption, mitigate AMR, and improve economic outcomes remain limited. This review critically examines non-antibiotic therapies for bovine mastitis, with particular emphasis on intramammary delivery systems and the obstacles hindering their clinical adoption. Finally, the article highlights existing knowledge gaps regarding pharmacodynamics, pharmacokinetics, tissue safety, and large-scale field trials, and outlines future research pathways aimed at advancing practical applications and reducing dependency on antibiotics.