Fibromyalgia, also known as fibromyalgia syndrome (FM), is a rheumatic syndrome which is currently considered idiopathic and multifactorial. It causes an increase in muscle tension associated with stiffness, asthenia (loss of strength with fatigue), cognitive impairment, insomnia or sleep disorders and impaired sensitivity to stimuli. We performed a prospective evaluation of 149 patients suffering from fibromyalgia syndrome according to the 2010 ACR Criteria. Patients were clinically assessed at baseline and after 1-3-6 months, using the patient-reported outcomes thermometer - 5-item scale (5TPROs). In addition to their therapy, all patients received a supplementation with Spilanthes Achmella. This food supplement is characterized by synergy of bioactive compounds, such as Acmella oleracea extract, and has neurotrophic, anti-inflammatory and pain-relieving effects. All patients were randomized at baseline to receive Spilanthes Achmella, 2 tablets per day for one month and subsequent tapering to 1 tablet per day for 5 months. At six months, a statistically significant difference in the following parameters was shown: pain P<0.001, fatigue P<0.001, physical function P<0.001, depression: P<0.001, general health P<0.001. Conversely, the post-hoc analysis data did not report any significant difference for the parameters between the third and sixth month. A drug-sparing effect was observed (P<0.001). The posthoc analysis revealed a significant difference between T0 and T3 P=0.00066 and between T0 and T6 P=0.00008. Our data indicate that supplementation with Spilanthes Achmella may lead to a significant improvement in pain, fatigue, physical function, depression and general health in fibromyalgia syndrome.