Background: Melissa officinalis standardised extracts, characterised by the presence of hydroxycinnamic acids, have been experimentally demonstrated to be endowed with anti-anxiety and anti-insomnia pharmacological actions. These effects, probably attributable, at least in part, to the role played by rosmarinic acid on GABA-T, have not always been observed in a reproducible manner in humans, perhaps due to the poor bioavailability of these compounds. Methods: as nutraceuticals and botanicals could be an alternative option to prescription medications for alleviating symptoms of mild anxiety and insomnia, we have verified in a prospective, double-blind, placebo-controlled, and cross-over study the supporting role on sleep quality played by a Melissa officinalis highly standardised extract, formulated as Phytosome™ (MOP) to improve the oral bioavailability of its active polyphenolic components. Results: results showed a significant reduction in the ISI score in the treated group, with an average of 6.8 ± 4.1 compared to 9.7 ± 3.7 in the placebo group, indicating a significant reduction of 2.9 points (p = 0.003). The SWS phase duration increased by an average of 15%, while the REM phase decreased by 10%. Additionally, 87% of participants in the treated group reported improved sleep quality, compared to 30% in the placebo group, with significant differences measured by chi-square test (χ2(4) = 21.01, p = 0.0003), highlighting the effects due to Melissa officinalis L. No significant changes in physical activity or anxiety levels were observed. Conclusions: these findings suggest that MOP may represent a natural and safe alternative to traditional pharmacological treatments for insomnia.