Background: Electromagnetic Field Intolerance Syndrome (EMFIS), also termed Idiopathic Environmental Intolerance (IEI) attributed to Electromagnetic Fields (IEI-EMF) by WHO, is a newly identified pathological disorder occurring in electrohypersensitivity (EHS) self-reporting patients. To date, there has been no recognized treatment of this disorder. We have shown that EHS self-reporting patients experience some degree of oxidative stress, inflammation, and autoimmune response. Additionally, Fermented Papaya Preparation (FPP) has some antioxidant, anti-inflammation, and immuno-modulating properties. The objective of this phase I-II clinical trial was thus to test whether FPP treatment is well tolerated, can improve clinical outcomes, and normalize biological abnormalities. Methods: 32 EMFIS-bearing patients were serially included in this trial, among which 26 and 16 of them were evaluable after 3 and 6 months of FPP treatment, respectively. Clinical assessment was conducted during a specific face to face interview by using a validated pre-established questionnaire. Biological assessment consisted of measuring intracerebral tissue pulsometric index (PI) in the temporal lobes with ultrasonic cerebral tomosphygmography (UCTS), in addition to oxidative stress and inflammation with a battery of oxidative stress and inflammation-related peripheral blood tests.Results: Overall clinical improvement was obtained in 50-60% of the cases, among which 20-35% presented major improvement that mainly consisted of the regression of cognitive symptoms such as loss of short term memory, concentration, attention deficiencies, insomnia, and fatigue. This clinical improvement was objectively supported by a statistically significant normal recovery of mean PI in the temporal lobes and by a FPP-related antioxidative effect evidenced by a statistically significant decrease in malondialdehyde levels in the plasma (p<0.0001) and increase in the Glutathione peroxidase activity in red blood cells (p<0.01) in patients experiencing oxidative stress. Moreover, this trial evidenced some degree of FPP-related anti-inflammatory effects by demonstrating a statistically significant decrease in histamine (p=0.049) and HSP27/HSP70 chaperone proteins (p=0.007) in the peripheral blood of patients with initial increased values of these inflammation-related biomarkers.Conclusion: The results suggest a beneficial clinical and biological therapeutic effect of FPP in EHS self-reporting patients. However, the precise underlying mechanism has not yet been elucidated.