© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.Objectives: This multicenter study aimed to evaluate the effects of St. John’s wort oil and virgin olive oil on the postoperative complications and compare this with chlorhexidine gluconate plus benzydamine hydrochloride mouthwash after the removal of impacted third molar. Methods: A total of 90 patients in need of impacted third molar surgery were included in this study. All included patients were randomly divided into 3 groups. The patients in group 1 received St. John’s wort oil; the patients in group 2 received virgin olive oil, and those in group 3 received mouthwash containing chlorhexidine gluconate plus benzydamine hydrochloride. The self-reported pain and difficulty during jaw function, trismus, facial swelling, number of analgesics used during first postoperative week, and postoperative periodontal condition including plaque accumulation, bleeding on probing, and periodontal pocket depth were compared between the groups. Results: No significant differences were found regarding the study variables. Conclusions: The data of the present study supports that the use of essential oils provides efficient alternative to the gold standard chlorhexidine gluconate mouthwash in reducing postoperative complications and improving healing process without adverse effects after surgical removal of impacted third molars. Clinical relevance: The use of essential oils showed similar results as the chlorhexidine gluconate mouthwash regarding swelling, mouth opening, pain, need for rescue medication, infectious complications (i.e., alveolar osteitis), and periodontal healing. Therefore, essential oils can be an alternative to routine mouthwashes to ensure oral hygiene after impacted third molar surgery.