Acmella oleracea (L.) R. K. Jansen (Asteraceae) is a plant species widely used in traditional Amazonian medicine to treat sexual dysfunction. The use of this plant has gained popularity because of its sensory properties, such as a tingling sensation. In this study on patients with premature ejaculation, we evaluated the clinical action of a nano-formulation containing an ethanolic extract of A. oleracea inflorescences. Major constituents in the extracts were identified based on gas chromatographic analysis. Participants used a spray preparation based on the A. oleracea extract for 12 weeks, during which they were instructed to apply the product 5 min prior to sexual intercourse. To assess therapeutic efficacy, participants were required to record the mean intravaginal latency time for ejaculation (IELT). During the period of spray treatment, the nano-formulation of A. oleracea increased participant IELT values (M = 293 s) compared with the baseline values (193 s). This nano-formulation reported clinical action in patients with premature ejaculation. It is accordingly considered to have potential application as a therapeutic alternative with benefits for both patients and their partners. Given the small number of participants in this study, further multicenter studies involving a larger number of participants are needed to confirm these observations.