Mild cognitive impairment (MCI) and early Alzheimer’s disease (AD) are characterized by blood–brain barrier (BBB) breakdown leading to abnormal BBB permeability ahead of brain atrophy ordementia. PreviousﬁndingsinADmousemodelshavereportedthebeneﬁcialeffectofextra-virgin oliveoil(EVOO)againstAD,whichimprovedBBBandmemoryfunctionsandreducedbrainamyloidβ (Aβ) and related pathology. This work aimed to translate these preclinical ﬁndings to humans in individuals with MCI. We examined the effect of daily consumption of reﬁned olive oil (ROO) and EVOO for 6 months in MCI subjects on BBB permeability (assessed by contrast-enhanced MRI), and brain function (assessed using functional-MRI) as the primary outcomes. Cognitive function and AD blood biomarkers were also assessed as the secondary outcomes. Twenty-six participants with MCI were randomized with 25 participants completed the study. EVOO signiﬁcantly improved clinical dementia rating (CDR) and behavioral scores. EVOO also reduced BBB permeability and enhanced functionalconnectivity. WhileROOconsumptiondidnotalterBBBpermeabilityorbrainconnectivity, it improved CDR scores and increased functional brain activation to a memory task in cortical regionsinvolvedinperceptionandcognition. Moreover,EVOOandROOsigniﬁcantlyreducedblood Aβ42/Aβ40 and p-tau/t-tau ratios, suggesting that both altered the processing and clearance of Aβ. In conclusion, EVOO and ROO improved CDR and behavioral scores; only EVOO enhanced brain connectivity and reduced BBB permeability, suggesting EVOO biophenols contributed to such an effect. This proof-of-concept study justiﬁes further clinical trials to assess olive oil’s protective effects against AD and its potential role in preventing MCI conversion to AD and related dementias.