Post-surgery complications increase morbidity, death, and healthcare expenses. Antibiotic prophylaxis is commonly used to prevent surgical site infections (SSIs) and other post-operative problems. This review study summarizes the research on prophylactic antibiotics in surgical patients. Introduction: SSIs are common and affect patient outcomes. It also discusses the dispute over prophylactic antibiotic timing, choice, and duration. SSI incidence and risk factors are discussed first. It emphasizes the importance of patient-related factors (age, obesity, smoking, and comorbidities), procedure-related factors (duration, contamination, and implantation), and healthcare-related factors (hospital environment, surgical team practices, and antibiotic prophylaxis) in the development of SSIs. Prophylactic antibiotic mechanisms and sensible use are discussed next. It describes how these antibiotics target pre-incision microorganisms to prevent colonization and infection. Selecting drugs based on expected infections and susceptibility patterns, timing, dose, and duration is rational use. Professional societies' antibiotic prophylaxis recommendations are then examined. These evidence-based guidelines standardize antibiotic selection, timing, and duration to improve patient safety and prevent antibiotic resistance. Antibiotic resistance and side effects are discussed next. Adverse effects include allergic reactions, gastrointestinal disturbances, and the risk of promoting antibiotic resistance. Antibiotic-resistant microorganisms emphasize the need for prophylactic antibiotics. The review concludes with preventative antibiotic options for the future. It suggests advances in surgical procedures, perioperative care, and bacterial pathogenesis. Novel antibiotics, combination therapy, microbial analysis-based tailored prophylaxis, and antimicrobial stewardship programs are future directions. High-risk patient populations, risk assessment algorithms, and preventive antibiotic treatments are under study. In conclusion, prophylactic antibiotics prevent post-surgical complications, especially SSIs. Further study is needed to enhance and individualize preventive antibiotic regimens for patient safety, efficacy, and antibiotic resistance prevention