Background: Third-molar extractions are common procedures often complicated by infections and alveolitis. The use of antibiotics as prophylaxis to prevent these complications is debated due to potential risks and side effects. Therefore, the aim of the present systematic review was to determine the efficacy of antibiotic prescription for the prevention of these complications. Methods: A comprehensive literature search was conducted in MEDLINE/PubMed, Cochrane, and SCOPUS databases up until June 2024. The focused question was “Does the antibiotic prescription influence the incidence of postoperative complications following third-molar extractions in healthy patients?” Systematic reviews assessing complications after third-molar extractions were included. Results: A total of 16 studies were included, revealing that antibiotic use significantly reduces infection risk and dry socket incidence compared to no prescription. Amoxicillin–clavulanic acid was particularly effective. Conclusions: Antibiotics, especially amoxicillin–clavulanic acid, are effective in preventing postoperative infections and alveolitis after third-molar extraction. However, their administration should be carefully considered to balance benefits against potential risks. Evidence supports the judicious use of antibiotics in dental surgery to optimize patient outcomes, minimizing possible adverse effects and the risk of developing antibiotic resistance.