Objective: Lower third impacted molar extraction, despite being a routinary procedure for oral and maxillo-facial surgeons, may often result in a significantly negative impact in patient’s post-operatory quality of life. Among others, treatments based on oxygen-enriched oils have been shown to provide valuable therapeutic benefits in promoting wound healing, and therefore improving the immediate post-operatory symptomatology. The aim of this triple-blinded randomized controlled study is to supplement the existing evidence in the scientific literature by assessing the effectiveness of NovoX^®-Drop (Moss S.p.A., Lesa, Novara), a specific type of oxygen enriched oil-based device in reducing pain and inflammatory stimulus of post-surgical wounds following the extraction of lower third impacted molars. Materials and methods: Seventy-one patients undergoing surgical extraction of a single lower third impacted molar were randomly assigned to receive either NovoX^®-Drop (Group A) or a glycerin-based gel (Group B). Additionally, both patient groups followed the same standard therapy with amoxicillin-clavulanic acid and ibuprofen. Data were collected preoperative (T0) and after three (T3) and seven (T7) days postoperative in order to assess the following outcomes: mean visual analogue scale (VAS) score during the seven days protocol treatment, total duration of nonsteroidal anti-inflammatory drug (NSAID) usage, trismus (maximum mouth opening) and facial oedema. Results: Group A (treatment group) reported significatively lower pain levels at T7 compared to group B (average VAS value during the week: Group A: 3.57 ± 0.39 cm; Group B: 4.47 ± 0.40 cm; p-value = 0.0014) despite a significatively shorter period of NSAID usage (average NSAID usage duration: Group A: 2.43 ± 0.38 days; Group B: 3.38 ± 0.44 days; p-value = 0.00001). Therefore, trismus seems to be better controlled in group A, although the difference between the groups did not reach the threshold for statistical significance. Conclusions: The results of this study suggest that application of NovoX^®-Drop is capable of significantly reducing the post-operatory pain as well as NSAID usage, representing a promising and effective option for third impacted molar extraction surgery management.