Background: Cystic fibrosis affects 1/3200 Caucasians. This genetic disease disturbs the ion and water homeostasis across epithelia, thus rendering mucus more viscous and harder to expel. Conventional treatments rely on the clapping method coupled with postural drainage. Despite the effectiveness of these procedures, they are invasive and enervating. Methods: Here we study a new mechano-acoustic treatment device to help patients expectorate excess mucus, the Frequencer™. We test both normal and pathological synthetic mucin solutions (1 % and 4 % by weight) in vitro. We varied the frequency applied (from 20 Hz to 60 Hz) as well as the amplitude (from 50 % to 100 % intensity). Moreover, we assessed the effect of NaCl on mucus rehydration. Results: A frequency of 40 Hz coupled with a 0.5 gL −1 NaCl solution provokes partial mucus rehydration, regardless of the amplitude selected, as the work of adhesion measurements evidenced. Conclusions: Mechanical solicitation is fundamental to help patients affected by cystic fibrosis expectorate mucus. With an operating frequency of 20 Hz to 65 Hz, the Frequencer™ provides a gentler therapy than traditional methods (conventional chest physiotherapy). The Frequencer™ proved to be effective in the homogenization of synthetic mucin solutions in vitro in 20 min and elicited improved effectiveness in a mucin-rich environment.