Hyperhomocysteinemia is an independent predictor of the risk for cognitive decline and may be a result of low levels of vitamins B(12) , B(6) , and folate. Previous findings suggest that adequate intake of these vitamins may reduce homocysteine levels. This review aimed to assess the effects of treatment with vitamins B(6,) B(12) , and/or folic acid in the homocysteine levels in patients with mild cognitive impairment (MCI). A systematic literature review was conducted in EMBASE, MEDLINE®, PsycINFO, and Cochrane Central Register of Controlled Trials. The research question was formulated using the Population, Intervention, Comparison, and Outcome (PICO) framework: in patients with MCI (P); what is the efficacy of vitamins B(6) , B(12) , and/or folic acid intake (I); compared with baseline values, and/or compared with controls (C); in reducing homocysteine levels from baseline (O). A total of eight primary studies with a total of 1,140 participants were included in the review. Four were randomized controlled trials, one was a quasi-controlled trial, and three were observational studies. All studies included folic acid in their intervention, seven vitamin B(12) , and four vitamin B(6) . Mean (SD) length of the intervention period was 18.8 (19.3) months, ranging from 1 to 60 months. All studies showed a statistically significant decrease in homocysteine levels in groups treated with vitamins B(6,) B(12) , and/or folic acid compared to controls, with a mean decline of homocysteine concentration of 31.9% in the intervention arms whereas it increased by 0.7% in the control arm. This review identified evidence of a reduction of plasma homocysteine levels in MCI patients taking vitamins B(6,) B(12) , and/or folic acid supplements, with statistically significant declines being observed after 1 month of supplementation. Findings support that supplementation with these vitamins might be an option to reduce homocysteine levels in people with MCI and elevated plasma homocysteine.