Background: Antimicrobial resistance has highlighted the need for effective infectious disease strategies. Antimicrobial stewardship programs (ASPs) may reduce antibiotic resistance, adverse reactions, and treatment failures. This systematic review examines ASPs in Saudi Arabia, assessing their efficacy, challenges, and outcomes to improve antimicrobial use and patient care. Methods: Searches were carried out in the Ovid, MEDLINE, Embase, PsycInfo, Scopus, and Web of Science Core Collection databases for studies published from 2007 to July 2024, in Saudi Arabia, following the PRISMA guidelines. Studies that assessed ASPs’ implementation, effectiveness, and outcomes in hospital settings were included. Results: Out of the 6080 titles identified, 14 studies met the inclusion criteria, covering different regions of the country, including Riyadh, Jeddah, Dhahran, Makkah, Al-Kharj, and a multi-regional study in Qassim and Riyadh. Various interventions were implemented by the ASPs, such as educational programs, audit and feedback, switching from intravenous to oral administration, and enhanced policies. These interventions collectively led to a decrease in the overall antimicrobial consumption and cost, and a reduction in cases with multidrug-resistant bacteria. Conclusions: The findings of this review highlight the positive impact of ASPs in Saudi Arabia. However, addressing challenges such as data limitations and training gaps is essential to enhance their effectiveness. Expanding education and refining implementation strategies are crucial for ensuring their long-term success.