Background & Objective: This systematic review evaluates the impact of guidelines on healthcare professionals' behavior and explores the resulting outcomes. Methods: Using PRISMA methodology, Scopus and Web of Science databases were searched, yielding 624 results. After applying inclusion criteria, 67 articles were selected for in-depth analysis. Results: The studies focused on key clusters: Target behaviors, Effectiveness, Research designs, Behavioral frameworks, and Publication outlets. Prescription behavior was the most studied (58.2 %), followed by other health-related behaviors (31.3 %) and hygiene practices (10.4 %). Significant behavior changes were reported in 46.3 % of studies, with 17.9 % showing negative effects, and 22.4 % reporting mixed results. Quantitative methods dominated (56.8 %), while qualitative methods (19.4 %) and review designs (13.4 %) were less common. Theoretical Domain Framework (TDF) and Behavior Change Wheel (BCW) were frequently used frameworks, with the UK and the USA contributing most studies. Medical doctors (44.8 %) were the primary participants, followed by general healthcare providers (37.3 %). Conclusions: The study highlights the varied effectiveness of guidelines, with prescription behavior being the most investigated. Guidelines influenced behavior positively in less than half of the cases, and doctors were the primary focus, rather than nurses. The complexity of interventions suggests a need for further research to develop more effective behavioral interventions and to standardize methodological approaches to reduce clinical variation in healthcare.