Antimicrobial resistance (AMR) is a growing global health crisis, threatening the effectiveness of antibiotics and other antimicrobial agents. The widespread misuse and overuse of antibiotics in healthcare, agriculture, and animal husbandry have accelerated the emergence of resistant pathogens, leading to increased morbidity, mortality, and economic burdens. This review critically examines existing global policies and best practices aimed at curbing AMR while proposing innovative, actionable strategies to mitigate its impact. The study explores the effectiveness of national and international AMR action plans, including the World Health Organization’s Global Action Plan (WHO-GAP) and country-specific frameworks such as the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria and the European One Health Action Plan against AMR. It evaluates regulatory policies, antibiotic stewardship programs, surveillance systems, and public awareness campaigns designed to promote responsible antimicrobial use. Key innovations in AMR reduction include the use of artificial intelligence (AI) and big data analytics for early detection of resistance patterns, precision medicine for targeted antimicrobial therapies, and the development of novel antibiotic alternatives such as bacteriophages and antimicrobial peptides. Additionally, advancements in rapid diagnostic tools and blockchain-based supply chain monitoring are examined for their potential to improve antimicrobial governance and reduce counterfeit medications. Challenges in implementing AMR policies, including regulatory fragmentation, lack of global coordination, and economic constraints, are discussed. The review highlights the need for interdisciplinary collaboration between governments, healthcare providers, pharmaceutical industries, and agricultural sectors to enforce stricter antimicrobial regulations, promote research and development of new treatments, and improve infection prevention measures. Findings suggest that a multifaceted approach integrating policy reforms, technological innovations, and public engagement is essential to slowing AMR progression. Strengthening surveillance networks, incentivizing antibiotic research, and enforcing antibiotic stewardship across all sectors can significantly reduce antimicrobial misuse and resistance. This review provides a roadmap for policymakers and stakeholders to develop sustainable, evidence-based AMR mitigation strategies.