AIM: We investigated the potential benefits of administering a nutraceutical combination of Bromelain (200 mg) and Boswellia serrata Casperome® (200 mg) on post-operative outcomes of hernioplasty with mesh. METHODS: One hundred eighty patients (27 females, 153 males) were enrolled to undergo open tension-free hernioplasty with the use of Progrip®. Patients were randomized to receive either one tablet of Siben® (study group) or placebo (control group) on an empty stomach, every twelve hours for eleven postoperative days. All patients filled out a medical questionnaire focused on postoperative pain, based on the Visual Analogue Scale (VAS) scale and the Short Form-36 (SF-36) questionnaire, at time T0 (day of surgery) and T28 (28th day after surgery). RESULTS: One-year results showed a significant improvement in the primary postoperative outcome in the study group. Perception of pain was significantly reduced in the Siben® group compared with controls, both on the seventh (p < 0.05) and the twenty-first (p < 0.05) postoperative day. Patients included in the Siben® group also resumed daily activities and returned to work earlier than the controls. Moreover, results of the SF-36 indicated better Quality of Life (QoL) scores in the study group compared to the placebo group. CONCLUSIONS: Our analysis effectively demonstrates that the use of Siben® in open inguinal hernia mesh repair may improve short- and long-term surgical outcomes, contributing to a better QoL.