The aim of this study is to evaluate the efficacy of taking a daily supplement based on active compounds (AUDISTIM® Day Night: A D/N) in alleviating tinnitus-related disability, as suggested by previous real-life studies. This double-blind randomized placebo-controlled study was conducted in adult with mild to severe tinnitus receiving a 3 month-supplementation. Tinnitus-related handicap (THI), psychological stress (MSP-9) and sleep quality (PSQI) were assessed at baseline and during intervention, perceived impression of tinnitus improvement at the end of the follow-up. The full set analysis included 114 patients (59 A D/N, 55 placebo) aged 53.8±11.4 years, 58% women, with fluctuating (45%) or permanent (55%) tinnitus from 9.3±9.4 years. A D/N supplementation led to greater changes in THI (-13.2±16.0 vs -6.2±14.4, p=0.0158, Cohen’s d=0.44) at 3 months, especially with continuous tinnitus (-15.0±16.3 vs -4.6±12.8, p=0.0065), and, to a lesser extent, at 1 month (-9.8±13.1 for A vs -4.3±12.1, p=0.0213). PSQI significantly improved over time in both groups, MSP-9 only with A D/N. In lines with previous observational studies, both clinical (THI score > 7 pts) and statistical (vs. placebo) improvement, more pronounced in permanent tinnitus, demonstrate the effectiveness of the combination of active compounds and support its use in the management of mild to severe tinnitus.